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Aluminium and human breast diseases
Abstract
The human breast is exposed to aluminium from many sources including diet and personal care products, but dermal application of aluminium-based antiperspirant salts provides a local long-term source of exposure. Recent measurements have shown that aluminium is present in both tissue and fat of the human breast but at levels which vary both between breasts and between tissue samples from the same breast. We have recently found increased levels of aluminium in noninvasively collected nipple aspirate fluids taken from breast cancer patients (mean 268 ± 28 μg/l) compared with control healthy subjects (mean 131 ± 10 μg/l) providing evidence of raised aluminium levels in the breast microenvironment when cancer is present. The measurement of higher levels of aluminium in type I human breast cyst fluids (median 150 μg/l) compared with human serum (median 6 μg/l) or human milk (median 25 μg/l) warrants further investigation into any possible role of aluminium in development of this benign breast disease. Emerging evidence for aluminium in several breast structures now requires biomarkers of aluminium action in order to ascertain whether the presence of aluminium has any biological impact. To this end, we report raised levels of proteins that modulate iron homeostasis (ferritin, transferrin) in parallel with raised aluminium in nipple aspirate fluids in vivo, and we report overexpression of mRNA for several S100 calcium binding proteins following long-term exposure of MCF-7 human breast cancer cells in vitro to aluminium chlorhydrate.
... All of these disruptions can lead to developing breast cancer. Own work based on [9,35,36]. ...
... Al compounds can interfere with the binding of estradiol to ERs in normal cells, but the exact mechanism of this process is still not fully understood. Tests have also been carried out to examine the effect of Al on the estrogen-dependent breast adenoma cell line MCF-7 [35]. It was shown that Al can interfere with the action of steroid hormones in a way typical for xenoestrogens. ...
... Darbre et al. [35], in their studies, showed that Al in the form of aluminum chlorohydrate (ACH) interfered with the functioning of ERs. Moreover, they indicated that long-term exposure of human breast epithelial cells MCF-10A to Al chloride or Al chlorohydrate may cause a decrease in mRNA levels. ...
The etiopathogenesis of breast cancer depends on genetic conditions, but recently more attention has been paid to the dependence of BC on certain environmental factors, for example, metalloestrogens, which include aluminum (Al) contained in antiperspirants used daily. The use of Al derivatives in antiperspirants in concentrations specified by the FDA, as well as European regulations (SCCS, 2020), do not classify Al as a hazardous and carcinogenic substance for humans. However, Al used to treat excessive sweating raises concerns, as many in vitro studies indicate that it can cause gene instability, change gene expression or increase oxidative stress, and also affect the body’s hormonal balance as a metalloestrogen. The environmental reality is that the breast is constantly exposed to many different chemicals, such as Al. This article reviews the literature to determine whether Al-based products can harm the body, as there are many facts and myths on the subject. The aim of the study is to present the current state of knowledge on the use of aluminum antiperspirants and the risk of breast cancer (BC). The article is based on data from the scientific literature, published in the PubMed and Google Scholar databases, as well as Science Direct, Scopus, Ovid MEDLINE, Ovid EMbase. It includes articles published in the years 2003–2023 mainly in English. Literature databases regarding human and animal studies were searched. To sum up, evaluating the effect of Al as a risk factor for breast cancer requires many studies using different research models focused on long-term exposure to Al-containing antiperspirants. Consumers are advised to limit their exposure to Al by making a conscious choice to minimize exposure to this compound.
... Alzheimers disease, encephalopathy) 2 and cancer. 3 Aluminium salt additives may also cause respiratory problems and induce anaphylactic shock in susceptible individuals. 2 There are also concerns about chronic exposure to triclosan, a common bacterial growth inhibitor in many deodorants, due to reports of dermal irritation and allergies. ...
... Alzheimers disease, encephalopathy) 6 and cancer. 3 Chronic exposure, as is the case with long term daily use in body odour management, may also result in structural and functional degradation of eccrine sweat ducts and the loss of secretory functionality. 26 Similarly, there is concern about including triclosan (and other deodorant compounds) in commercial deodorants as they have also been linked to a myriad of serious health problems. ...
... Alzheimers disease, encephalopathy) 2 and cancer. 3 Aluminium salt additives may also cause respiratory problems and induce anaphylactic shock in susceptible individuals. 2 There are also concerns about chronic exposure to triclosan (a common bacterial growth inhibitor in many deodorants) due to reports of dermal irritation and allergies. ...
... Alzheimers disease, encephalopathy) 6 and cancer. 3 Chronic exposure, as is the case with long term daily use in body odour management, may also result in structural and functional degradation of eccrine sweat ducts and the loss of secretory functionality. 38 Similarly, there is concern about including triclosan (and other deodorant compounds) in commercial deodorants as they have also been linked to a myriad of serious health problems. ...
Introduction: Many high antioxidant fruit extracts can inhibit the growth of
multiple bacterial pathogens. They may also inhibit the growth of malodour
producing bacteria and thus be useful deodorant components, although
this is yet to be tested for many Australian native fruits. Materials and
Methods : Methanolic and aqueous K. pomifera and P. elatus fruit extracts
were investigated by disc diffusion and liquid dilution MIC assays against
the most significant bacterial contributors to axillary and plantar malodour.
Toxicity was determined using Artemia franciscana nauplii bioassays
and unbiased HPLC-MS QTOF analysis was used to identify interesting
consituents of the most active extract. Results: Methanolic and aqueous K.
pomifera and P. elatus fruit extracts displayed noteworthy bacterial growth
inhibitory activity against all of the malodour forming bacteria tested. The
methanolic K. pomifera extract had particularly good antibacterial effects,
strongly inhibiting the growth of all bacteria, with MIC values substantially
less than 1000 μg/mL. Indeed, liquid dilution (LD) MIC values of 610, 894,
663 and 625 μg/mL were recorded against C. jeikeium, P. acnes, B. linens and
S. epidermidis respectively. Similar, albeit slightly higher LD MIC values
were noted for the aqueous K. pomifera fruit extract, and for the methanolic
and aqueous P. elatus fruit extracts against these bacteria. All K. pomifera
and P. elatus fruit extracts were non-toxic in the Artemia fransiscana
bioassay. Several interesting phytochemicals, including several tannins,
were identified in the methanolic K. pomifera fruit extract. Conclusion:
The lack of toxicity of the methanolic and aqueous K. pomifera and
P. elatus fruit extracts and their noteworthy growth inhibition of axillary and
plantar malodour producing bacteria indicate their potential as deodorant
components. Further studies are warranted to isolate and identify the
active components and to determine the antibacterial mechanism.
... Alzheimers disease, encephalopathy) 2 and cancer. 3 Aluminium salt additives may also cause respiratory problems and induce anaphylactic shock in susceptible individuals. 2 There are also concerns about chronic exposure to triclosan, a common bacterial growth inhibitor in many deodorants. ...
... Alzheimers disease, encephalopathy) 6 and cancer. 3 Chronic exposure, as is the case with long term daily antiperspirant usage, can also result in structural and functional degradation of eccrine sweat ducts and the loss of secretory functionality. 34 • Inhibition/reduction of the bacteria which cause axillary and/ or plantar malodours. ...
Introduction: Tasmannia spp. extracts inhibit the growth of many bacterial
pathogens. They may also inhibit the growth of malodour producing
bacteria and thus be useful deodorant components, although this is yet
to be tested. Methods: T. lanceolata and T. insipida fruit and leaf solvent
extracts were investigated by disc diffusion and liquid dilution MIC
assays against the most significant bacterial contributors to axillary and
plantar malodour formation. Toxicity was determined using the Artemia
franciscana nauplii bioassay. Non-targeted HPLC separation of the
T. lanceolata methanolic berry extracts, coupled to high resolution timeof-
flight (TOF) mass spectroscopy was used for the identification and
characterisation of individual components in the extract. Results: The
methanolic and aqueous T. lanceolata and T. insipida fruit and leaf extracts
displayed noteworthy bacterial growth inhibitory activity against all of
the malodour forming bacteria tested. The T. lanceolata methanolic fruit
extract was particularly potent, with low MIC values recorded against
C. jeikeium (480μg/mL) and S. epidermidis (513μg/mL), as well as moderate
activity against P. acnes (1750μg/mL) and B. linens (1250μg/mL). Similar
MIC values were noted for the aqueous T. lanceolata fruit extract against
C. jeikeium and S. epidermidis, although this extract was ineffective against
the other bacteria tested. Similar, albeit less potent inhibitory profiles were
noted for the T. lanceolata and T. insipida leaf extracts against C. jeikeium
and S. epidermidis. All Tasmannia spp. extracts were nontoxic in the
Artemia fransiscana bioassay. Non-biased phytochemical analysis of the
methanolic leaf extract highlighted several notable compounds, including
polygodial, capsidiol, salutarisolide gallic acid and combretastatin A1 in
relative abundance. Conclusion: The lack of toxicity of the T. lanceolata
and T. insipida fruit and leaf extracts and their potent growth inhibition of
axillary and plantar malodour producing bacteria indicate their potential as
deodorant components.
... Aluminum has an active role in some neurodegenerative diseases, such as amyotrophic lateral sclerosis or Alzheimer's and Parkinson's dementia. [2,[7][8][9][10][11][12][13][14]. The toxicity of Al also has an effect on mineral nutrient uptake and the composition in plants. ...
... The mobility, toxicity, and bioavailability of aluminum mainly depend on the form in which this element appears [18]. Other factors such as pH value, the type of a ligand, temperature, and reaction time also have effects on aluminum chemistry [14]. The most toxic form of this elements for living organisms is inorganic aluminum-Al 3+ , AlOH 2+ , Al(OH)2 + , and so on [19,20]. ...
Aluminum is very common in the natural environment and in everyday human life. We are living in the “aluminum age.” Its average daily intake should not exceed a few mg/day. Unfortunately, despite the growing number of alarming data about the toxicity of this element, human exposure to aluminum is constantly increasing. The toxicity and bioavailability of aluminum depends mainly on the form in which it occurs. The main variables conditioning the form are the concentration, the type, the molar ratio of aluminum to ligand, the pH value, and the temperature. This research presents a new method for speciation analysis of both inorganic and organic aluminum complexes in model solutions by LC–ICP–MS. Different solutions with variable pH values and different Al/ligand molar ratios (fluorides and several organic ligands, e.g., citrates and oxalates ions) were used. The chromatographic separation process was carried out based on isocratic and gradient elution, using a cation exchange analytical column. All determinations have been confirmed based on chemical equilibrium modeling programs. The new developed method was successfully applied for the first time in speciation analysis of real samples: white and red wine.
... It has been demonstrated that breast tumors accumulate aluminum ions, and this applies to both humans and animals (Majewska et al. 1997;Skibniewska 2010). Most probably, this is related with biochemical properties of a given cancer tissue, which are characterized by overexpression of osteopontin, which forms complexes with aluminum ions; these act in two ways: on estrogen receptors and through binding with DNA in the cells of the mammary gland, which results in genomic instability (Banasik et al. 2013;Pereira et al. 2013;Darbre et al. 2011Darbre et al. , 2013. Aluminum salts act as a catalyst of Fenton's reaction, which produces free radicals damaging cellular structures. ...
... Besides its effect on the genome, aluminum has the ability to bind to estrogen receptors; hence it is referred to as metalloestrogen. The signs of its activity include an impact on estrogen-dependent gene expression in response to the activity of these hormones (Darbre et al. 2011(Darbre et al. , 2013. Moreover, aluminum interacts with other elements. ...
Aluminum is the third most abundant element in nature, after oxygen and silicon. Its content in the Earth’s crust has been estimated at a level of 8%. In spite of this, the element has never been engaging in the metabolic processes of the evolving living organisms. Aluminum reaches the body of an animal mostly ingested with food. Crossing the intestinal barrier, the metal gets to the bloodstream and so is transported to various tissues using the iron-transport routes. Of the total aluminum uptake, the majority is deposited in the bone (60%) and lungs (25%), whereas much lower amounts accumulate in the muscles (10%) and the liver (3%). Cerebral accumulation of the total uptake is about 1%. Besides blood, the metal is also found in all the other body fluids of a homeothermic organism, e.g., cerebrospinal fluid, lymph, semen, sweat, or urine. Studies on aluminum toxicity involving various taxonomic groups enable concluding that the mechanisms are similar across the taxa and consist mainly in evoking oxidative stress in cells. At the cellular level, aluminum reacts with cell membranes, cytoskeletal structures, and nucleic acids. In terrestrial vertebrates, aluminum impact results in altered enzymatic activity in the central nervous system and other organs and systems of the body. The metal affects the bone tissue metabolism, impairs the function of the excretory system and liver, and also has a negative effect on erythropoiesis. Human activity observed over the last centuries has led to a rapid growth in the production of aluminum obtained from the natural sources and, as a result, to its inclusion into the trophic chains of various ecosystems. In consequence, since 1970, aluminum has been treated as a xenobiotic accumulating in living organisms, whose bioavailability is continuously increasing.
... Moreover, it has been demonstrated that ferritin in plasma from AD patients, particularly those with mild AD, contains significantly higher concentrations of aluminium compared with plasma ferritin from age-and sex-matched controls which, given the pivotal role of this protein in the regulation of metal homeostasis, may be a crucial finding; the finding of a higher level in mild AD compared with severe AD may also point to a first phase in which there is an aluminium overload of ferritin, followed by a phase in which ferritin with reduced functional capacity releases aluminium (De Sole et al. 2013). Interestingly, the capacity of aluminium to disrupt the activity of ferritin and transferrin, with the subsequent disruption of iron homeostasis, has been demonstrated in a series of studies implicating aluminium as a potential causative agent in certain types of breast cancer cells as well as in primary invasive breast cancers and ductal carcinoma in situ (Darbre et al. 2013;Darbre et al. 2011;Mannello et al. 2013). ...
... Oxidative damage as evidenced by increased lipid peroxidation and depleted anti-oxidant defences induced by prolonged aluminium exposure appears to be focused in the prefrontal cortex, cerebellum, hippocampus and brainstem (Yuan et al. 2012;Kumar et al. 2011). It is also noteworthy that several authors have reported a linear relationship between increased cellular levels of aluminium and concentrations of protein carbonyls and S100 proteins Darbre et al. 2013;Darbre et al. 2011). This is of particular interest as these molecules may function as DAMPs and cause chronic stimulation of PRRs and hence be a source of chronic immune activation as discussed above. ...
The conceptualisation of autistic spectrum disorder and Alzheimer’s disease has undergone something of a paradigm shift in recent years and rather than being viewed as single illnesses with a unitary pathogenesis and pathophysiology they are increasingly considered to be heterogeneous syndromes with a complex multifactorial aetiopathogenesis, involving a highly complex and diverse combination of genetic, epigenetic and environmental factors. One such environmental factor implicated as a potential cause in both syndromes is aluminium, as an element or as part of a salt, received, for example, in oral form or as an adjuvant. Such administration has the potential to induce pathology via several routes such as provoking dysfunction and/or activation of glial cells which play an indispensable role in the regulation of central nervous system homeostasis and neurodevelopment. Other routes include the generation of oxidative stress, depletion of reduced glutathione, direct and indirect reductions in mitochondrial performance and integrity, and increasing the production of proinflammatory cytokines in both the brain and peripherally. The mechanisms whereby environmental aluminium could contribute to the development of the highly specific pattern of neuropathology seen in Alzheimer’s disease are described. Also detailed are several mechanisms whereby significant quantities of aluminium introduced via immunisation could produce chronic neuropathology in genetically susceptible children. Accordingly, it is recommended that the use of aluminium salts in immunisations should be discontinued and that adults should take steps to minimise their exposure to environmental aluminium.
... Currently, antibacterial agents such as quaternary ammonium compounds like triclosan, aluminum salts, and aromatic odor-masking agents are used in most deodorant items. These ingredients have been discussed in the context of a potential contribution to breast or prostate cancer (Bedoux et al., 2012;Darbre et al., 2011;McLachlan & Van Berkum, 1986). Hence, there is an interest in using herbal products that have antibacterial effects against the most common odor-inducing bacteria (Benohanian, 2001;Weckesser et al., 2007). ...
The use of plants as a source of active principles for cosmetics has significantly increased in the last few years. Safety, compatibility with all types of skin, fewer side effects, and availability are among the advantages of herbal cosmetics above synthetic ingredients. The present review aims to explore the most important plants used in cosmetics. A literature search was carried out in several electronic databases with the following phrases: skincare and plants; cosmetics and plants; natural and cosmetics; and natural and skincare. Furthermore, more detailed filters such as clinical studies, meta-analyses, and systemic reviews were applied to positive results. Various plants and plant extracts currently used in skin care, scaring, whitening, and aging, as well as in sun protection, acne, eczema, and others, have been included in this review. The effectiveness of these plants is based mainly on preclinical research, and to a lesser extent on clinical studies. Some plant extracts or oils have been tested clinically, such as onions, aloe, and tea tree oil, more than other plant extracts. Despite many studies on natural products to improve dermal needs, proper clinical cosmeceutical trials are much fewer than expected. Therefore, more clinical trials are needed to evaluate appropriate efficacy. Furthermore, new formulation technologies might enhance the cosmeceutical benefits, but more work is warranted.
... CP-4 is normally used for the production of dental implants, whereas Ti-64 ELI alloy is applied as an abutment material. Lately, especially the use of Ti-64 ELI in implant applications has been intensively discussed as aluminum (Al) is suspected to cause several diseases such as breast cancer (Darbre et al., 2011), dementia, and Alzheimer's disease (Mirza et al., 2017). In addition, vanadium and vanadium ions as well as its oxides are cytotoxic (Geetha et al., 2009). ...
In dentistry, the most commonly used implant materials are CP-Titanium Grade 4 and Ti-6Al-4V ELI, possessing comparably high Young’s modulus (>100 GPa). In the present study, the second-generation titanium alloy Ti-13Nb-13Zr is investigated with respect to the production of advanced dental implant systems. This should be achieved by the fabrication of long semi-finished bars with high strength and sufficient ductility to allow the automated production of
small implants at low Young’s modulus (<80 GPa) to minimize stress shielding, bone resorption, and gap formation between the bone and implant. In addition, bacterial colonization is to be reduced, and bone adhesion is to be enhanced by adjusting the microstructure. To do so, a dedicated thermo-mechanical treatment for Ti-13Nb-13Zr has been developed. This includes the adaption of equal channel angular swaging, a modern process of severe plastic deformation to continuously manufacture nanostructured materials, to Ti-13Nb-13Zr and short-time recrystallization and ageing treatments. In particular, two-pass equal channel angular swaging at a deformation temperature of 150°C and a counterpressure of 8 MPa has successfully been used to avoid shear band formation during
deformation and to produce long Ti-13Nb-13Zr bars of 8mm diameter. During a recrystallization treatment at 700°C for 10 min followed by water quenching, a sub-micron-size primary α-phase in a matrix of α″-phase was developed. Subsequent ageing at 500°C for 1 h leads to martensite decomposition and, thus, to a homogeneously nanostructured microstructure of α- and β-phase
with substructures smaller than 200 nm. The resulting mechanical properties, especially the ultimate tensile strength of more than 990 MPa, fulfill the requirements of ASTM F1713 at Young’s modulus of 73 GPa. Biological investigations show promising results in reducing bacterial biofilm formation and increased cell proliferation of osteoblasts compared to CP-Titanium Grade 4 and Ti-6Al-4V ELI, especially, if etched surfaces are applied.
... CP-4 is normally used for the production of dental implants, whereas Ti-64 ELI alloy is applied as an abutment material. Lately, especially the use of Ti-64 ELI in implant applications has been intensively discussed as aluminum (Al) is suspected to cause several diseases such as breast cancer (Darbre et al., 2011), dementia, and Alzheimer's disease (Mirza et al., 2017). In addition, vanadium and vanadium ions as well as its oxides are cytotoxic (Geetha et al., 2009). ...
In dentistry, the most commonly used implant materials are CP-Titanium Grade 4 and Ti-6Al-4V ELI, possessing comparably high Young’s modulus (>100 GPa). In the present study, the second-generation titanium alloy Ti-13Nb-13Zr is investigated with respect to the production of advanced dental implant systems. This should be achieved by the fabrication of long semi-finished bars with high strength and sufficient ductility to allow the automated production of small implants at low Young’s modulus (<80 GPa) to minimize stress shielding, bone resorption, and gap formation between the bone and implant. In addition, bacterial colonization is to be reduced, and bone adhesion is to be enhanced by adjusting the microstructure. To do so, a dedicated thermo-mechanical treatment for Ti-13Nb-13Zr has been developed. This includes the adaption of equal channel angular swaging, a modern process of severe plastic deformation to continuously manufacture nanostructured materials, to Ti-13Nb-13Zr and short-time recrystallization and ageing treatments. In particular, two-pass equal channel angular swaging at a deformation temperature of 150°C and a counterpressure of 8 MPa has successfully been used to avoid shear band formation during deformation and to produce long Ti-13Nb-13Zr bars of 8 mm diameter. During recrystallization treatment at 700°C for 10 min followed by water quenching, a sub-micron-size primary α-phase in a matrix of α″-phase was developed. Subsequent ageing at 500°C for 1 h leads to martensite decomposition and, thus, to a homogeneously nanostructured microstructure of α- and β-phase with substructures smaller than 200 nm. The resulting mechanical properties, especially the ultimate tensile strength of more than 990 MPa, fulfill the requirements of ASTM F1713 at Young’s modulus of 73 GPa. Biological investigations show promising results in reducing bacterial biofilm formation and increased cell proliferation of osteoblasts compared to CP-Titanium Grade 4 and Ti-6Al-4V ELI, especially, if etched surfaces are applied.
... Similarly, the breast milk samples obtained from the women who reported frequent use of deodorants contained higher aluminum levels compared to those obtained from women who reported less frequent use. It has been argued that the application of aluminumbased antiperspirants to the underarm area and adjacent to the breasts could particularly present a continuous source of exposure to aluminum [36]. On the other hand, the findings reported in this study contradicted those reported in a recent study in which the use of aluminum-based antiperspirants did not increase aluminum contents in breast milk [37]. ...
This study assessed aluminum concentrations in breast milk samples obtained from breastfeeding women in resource-limited countries, estimated daily intake of aluminum by breastfed infants, and identified predictors of higher breast milk aluminum concentrations. A descriptive analytical approach was used in this multicenter study. Breastfeeding women were recruited from different maternity health clinics in Palestine. Aluminum concentrations in 246 breast milk samples were determined using an inductively coupled plasma-mass spectrometric method. The mean breast milk aluminum concentration was 2.1 ± 1.5 mg/L. The mean estimated daily intake of aluminum by infants was 0.37 ± 0.26 mg/kg body weight/day. Multiple linear regression showed that breast milk aluminum concentrations were predicted by living in urban areas, closer to industrial areas, waste disposals, frequent use of deodorants, and less frequent use of vitamins. Breast milk aluminum levels among Palestinian breastfeeding women were comparable to those previously determined in occupationally unexposed women.
... The potential systemic toxicity of aluminum-based antiperspirants via dermal application has been a matter of concern over the years as several studies have implicated these products as contributory factors in the development of breast cancer and neurodegenerative diseases (e.g., Alzheimer's disease) (Darbre et al., 2011(Darbre et al., , 2013Exley et al., 2007;Farasani & Darbre, 2015;Linhart et al., 2017;Sappino et al., 2012). However, aluminum salts have shown to be poorly absorbed through the skin and the daily use of aluminum-based antiperspirants is not believed to contribute to systemic exposure. ...
Aluminum chlorohydrate (ACH) is a major aerosol component frequently used as the active ingredient in antiperspirants, and in vivo studies have raised a concern about its inhalation toxicity. Still, few studies have addressed its effects on the human respiratory tract. Therefore, we developed a study on ACH inhalation toxicity using an in vitro human alveolar cell model (A549 cells) with molecular and cellular markers of oxidative stress, immunotoxicity, and epigenetic changes. The chemical characterization of ACH suspensions indicated particle instability and aggregation; however, side‐scatter analysis demonstrated significant particle uptake in cells exposed to ACH. Exposure of A549 cells to non‐cytotoxic concentrations of ACH (0.25, 0.5 and 1 mg/mL) showed that ACH induced reactive oxygen species. Moreover, ACH upregulated TNF, IL6, IL8 and IL1A genes, but not the lncRNAs NEAT1 and MALAT1. Finally, no alterations on the global DNA methylation pattern (5‐methylcytosine and 5‐hydroxymethylcytosine) or the phosphorylation of histone H2AX (γ‐H2AX) were observed. Our data suggest that ACH may induce oxidative stress and inflammation on alveolar cells, and A549 cells may be useful to identify cellular and molecular events that may be associated with adverse effects on the lungs. Still, further research is needed to ensure the inhalation safety of ACH. Aluminum chlorohydrate (ACH) is an aerosol component used in antiperspirants, but its effects in the human respiratory tract are unclear. A549 cells were used as an in vitro cell model to investigate ACH lung toxicity. Despite instability and aggregation, ACH particle uptake was observed in A549 cells. Our results shows that ACH can increase reactive oxygen species and TNF, IL6, IL8 and IL1A mRNA in A549 cells. Our data may direct future research on the potential inhalation toxicity of ACH.
... Alloy development of the last decades aimed at the avoidance of aluminum (Al) and vanadium (V) in medical implant materials because of their potentially critical effects to the human health. Aluminum is suspected to cause breast cancer [2] and dementia as well as the Alzheimer disease [3]. Furthermore, vanadium and its oxides are cytotoxic [4]. ...
Nanostructured titanium plays an important role in biomedical applications, especially in dentistry, as the nanostructured surface promotes bone cell growth and simultaneously prevents bacterial colonization. Nanostructured microstructures can be obtained through Severe Plastic Deformation processes. In this paper, thermomechanical processing via Equal Channel Angular Swaging for the continuous production of nanocrystalline Ti–13Nb–13Zr (TNZ) is investigated with respect to applications in dental implantology. TNZ is a second-generation β-rich (α + β) medical alloy which can consist of the three phases α- and β-phase as well as αʺ-martensite. The αʺ-martensite has a very low Young’s modulus and a comparably low strength with high ductility allowing metal forming even at low temperatures. By adjusting different phase volume fractions, a wide range of mechanical properties can be realized, especially Young’s modulus between 50 and 90 GPa at a yield strength exceeding 950 MPa making it an ideal material for dental implants and abutments.
Graphical abstract
... The work of Mannello et al. (Figure S2) started with publications in the beginning of the 21st century and mostly focused on the biochemical constituents of nipple aspirate such as P-cadherin [93], proteins involved in the of lipid peroxidation and oxidative stress [94][95][96], C-reactive protein [97], and aluminum [98][99][100]. Methodologically, for these investigations, Mannello et al. usually compared NAF from cohorts of healthy women with cohorts of women with breast cancer; comparing biomarker concentrations between NAF, plasma, and serum. ...
Simple Summary
Nipple aspirate fluid (NAF) is a promising source of markers for detection of breast cancer. NAF can be acquired via the nipple by aspiration using a suction device, which is well tolerated by women. Future possible applications of biomarkers for breast cancer derived from NAF could be (1) as a detection tool to identify the initiation of the cancer development process, (2) as an additional tool next to imaging (mammography and breast magnetic resonance imaging) or (3) as a replacement tool for when imaging is not advisable for women, such as during pregnancy and breastfeeding. With this paper, we present a narrative review and perspectives of NAF research at a glance.
Abstract
Nipple aspirate fluid (NAF) is an intraductal mammary fluid that, because of its close proximity to and origin from the tissue from which breast cancer originates, is a promising source of biomarkers for early breast cancer detection. NAF can be non-invasively acquired via the nipple by aspiration using a suction device; using oxytocin nasal spray helps increase yield and tolerability. The aspiration procedure is generally experienced as more tolerable than the currently used breast imaging techniques mammography and breast magnetic resonance imaging. Future applications of NAF-derived biomarkers include their use as a tool in the detection of breast carcinogenesis at its earliest stage (before a tumor mass can be seen by imaging), or as a supporting diagnostic tool for imaging, such as when imaging is less reliable (to rule out false positives from imaging) or when imaging is not advisable (such as during pregnancy and breastfeeding). Ongoing clinical studies using NAF samples will likely shed light on NAF’s content and clinical potential. Here, we present a narrative review and perspectives of NAF research at a glance.
... Breast cancer patients had higher levels of Al in breast tissues than in blood serum (Darbre et al., 2013b). There were higher levels of Al in nipple aspirates of cancer patients than healthy controls and higher Al levels in breast cyst fluid than serum or milk (Darbre et al., 2011). The Al contents of nipple aspirates of breast cancer patients correlated with biomarkers of oxidative stress and inflammation in the breast microenvironment (Mannello et al., 2013). ...
Aluminium (Al) is frequently accessible to animal and human populations to the extent that intoxications may occur. Intake of Al is by inhalation of aerosols or particles, ingestion of food, water and medicaments, skin contact, vaccination, dialysis and infusions. Toxic actions of Al induce oxidative stress, immunologic alterations, genotoxicity, pro-inflammatory effect, peptide denaturation or transformation, enzymatic dysfunction, metabolic derangement, amyloidogenesis, membrane perturbation, iron dyshomeostasis, apoptosis, necrosis and dysplasia. The pathological conditions associated with Al toxicosis are desquamative interstitial pneumonia, pulmonary alveolar proteinosis, granulomas, granulomatosis and fibrosis, toxic myocarditis, thrombosis and ischemic stroke, granulomatous enteritis, Crohn’s disease, inflammatory bowel diseases, anemia, Alzheimer’s disease, dementia, sclerosis, autism, macrophagic myofasciitis, osteomalacia, oligospermia and infertility, hepatorenal disease, breast cancer and cyst, pancreatitis, pancreatic necrosis and diabetes mellitus. The review provides a broad overview of Al toxicosis as a background for sustained investigations of the toxicology of Al compounds of public health importance.
... Non-mercury metals in our breast samples that have previously been implicated in the pathogenesis of breast cancer were aluminium [43,[65][66][67], cadmium [10,24,68], iron [69,70], nickel [68], chromium [10] and lead [24,71]. However, we were unable to confirm the cellular location of these metals in our samples since reliable histochemical methods are not available to detect them, and cell-specific elemental techniques such as x-ray fluorescence microanalysis require the use of frozen sections. ...
Objective
Exposure to toxic metals such as mercury has been proposed to be a risk factor for the development of breast cancer since some metals can promote genetic mutations and epigenetic changes. We sought to find what toxic metals are present in normal breast tissue and in the tumours of women who had mastectomies for invasive ductal breast carcinoma.
Materials and methods
Formalin-fixed paraffin-embedded blocks from mastectomies for breast carcinoma were examined from 50 women aged 34–69 years. Paraffin blocks selected for elemental analysis were from breast tissue not involved by carcinoma and from the carcinoma itself. Seven micrometer-thick sections were stained with autometallography to demonstrate the presence of mercury, and subjected to laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) to confirm the presence of mercury and to detect other toxic metals.
Results
Autometallography-detected mercury was seen in intraductal secretions and some luminal epithelial cells of normal breast lobules in 26 (55%) of the 47 samples where lobules were present, and in 10 (23%) of carcinomas from the 44 samples where carcinoma was present. In eight samples ductal carcinoma in situ was present and one of these contained mercury. LA-ICP-MS confirmed the presence of mercury in samples that stained with autometallography, and detected lead, iron, nickel, aluminium, chromium and cadmium in some samples.
Conclusions
Mercury was present in normal breast lobules in more than half of mastectomy samples that contained an invasive carcinoma, and in a smaller proportion of carcinomas and ductal carcinomas in situ. Other toxic metals that may interact synergistically with mercury could be detected in some samples. These findings do not provide direct evidence that toxic metals such as mercury play a role in the pathogenesis of breast cancer, but suggest that future molecular biological investigations on the role of toxic metals in breast cancer are warranted.
... Breast cancer patients had higher levels of Al in breast tissues than in blood serum (Darbre et al., 2013b). There were higher levels of Al in nipple aspirates of cancer patients than healthy controls and higher Al levels in breast cyst fluid than serum or milk (Darbre et al., 2011). The Al contents of nipple aspirates of breast cancer patients correlated with biomarkers of oxidative stress and inflammation in the breast microenvironment (Mannello et al., 2013). ...
Aluminium (Al) is frequently accessible to animal and human populations to the extent that intoxications may occur. Intake of Al is by inhalation of aerosols or particles, ingestion of food, water and medicaments, skin contact, vaccination, dialysis and infusions. Toxic actions of Al induce oxidative stress, immunologic alterations, genotoxicity, pro-inflammatory effect, peptide denaturation or transformation, enzymatic dysfunction, metabolic derangement, amyloidogenesis, membrane perturbation, iron dyshomeostasis, apoptosis, necrosis and dysplasia. The pathological conditions associated with Al toxicosis are desquamative interstitial pneumonia, pulmonary alveolar proteinosis, granulomas, granulomatosis and fibrosis, toxic myocarditis, thrombosis and ischaemic stroke, granulomatous enteritis, Crohn's disease, inflammatory bowl diseases, anaemia, Alzheimer's disease, dementia, sclerosis, autism, macrophagic myofasciitis, osteomalacia, oligospermia and infertility, hepatorenal disease, breast cancer and cyst, pancreatitis, pancreatic necrosis and diabetes mellitus. The review provides a broad overview of Al toxicosis as a background for sustained investigations of the toxicology of Al compounds of public health importance.
... Aluminum is diversely affecting the growth rate of human brain cells. (Al Juhaiman, Al-Shihry, & Al-Hazimi, 2014;Al Zubaidy, Mohammad, & Bassioni, 2011;Bassioni et al., 2012;Darbre, Pugazhendhi, & Mannello, 2011;Gitelman, 1989;Kim & Clesceri, 2001;Rittirong & Saenboonruang, 2018). ...
The aim of the work was to estimate the degree of aluminum leakage from aluminum foil during baking process of selected food/meals. The experiment included 11 different types of food (Atlantic salmon Salmo salar, mackerel Scomber scombrus, duck breasts, cheese Hermelín, tomato, paprika, Carlsbad dumplings, pork roast, pork neck, chicken breasts, and chicken thighs) baked both marinated and not marinated. The aluminum content was measured by AAS and ICP/MS methods. The highest aluminum increase was observed in the samples of marinated Salmo salar (41.86 ± 0.56 mg/kg), Scomber scombrus (49.34 ± 0.44 mg/kg), and duck breast (117.26 ± 1.37 g/kg). The research was also supported by the survey that consisted of 784 respondents with different sociodemographic characteristics. The study clearly showed the occurrence of aluminum contamination of food when it is prepared by baking in aluminum foil. It cannot be concluded that aluminum leakage will occur with each type of food. The aluminum contents found among investigated samples are not alarming, though the increase was measured up to 40 times. On the other hand, revealed aluminum contents can represent a risk for younger/smaller children and for individuals with diagnosed certain ailments. The experiment included 11 different types of food (Atlantic salmon Salmo salar, mackerel Scomber scombrus, duck breasts, cheese Hermelín, tomato, paprika, Carlsbad dumplings, pork roast, pork neck, chicken breasts, and chicken thighs) baked both marinated and not marinated. The study showed the level of aluminum contamination of food when it is prepared by baking in aluminum foil. It cannot be concluded that aluminum leakage will occur with each type of food.
... encephalopathy, Alzheimer's disease), respiratory issues and anaphylaxis [7]. Furthermore, there is evidence suggesting that aluminium salts may increase the risk of developing cancer, although this is yet to be conclusively proven [8]. Similarly, adverse health issues (allergies, dermal irritation) have been reported when individuals were exposed to high concentrations of triclosan [9]. ...
Objective:
Recently, our group reported that extracts prepared from the Australian native plant Terminalia ferdinandiana Exell. are potent inhibitors of the growth malodorous bacteria with similar efficacy to triclosan and through these results, we highlighted a potential biological alternative to the current chemical additives. Other members of the genus Terminalia are also well documented for their antibacterial potential and tannin contents and thus were investigated as potential deodorant additives.
Methods:
Solvent extractions prepared from of selected Indian, Australian and South African Terminalia spp. were screened by disc diffusion and liquid dilution assays against C. jeikeium, S. epidermidis, P. acnes and B. linens. The antibacterial activity was quantified by liquid dilution MIC assays. The extracts were screened for toxicity using Atremia franciscana nauplii and HDF cell viability bioassays. High-resolution time-of-flight (TOF) LC-MS and GC-MS headspace fingerprint analysis was used to detect tannin, flavonoid and terpenoid components in the extracts.
Results:
Bacterial growth inhibition was observed in all Terminalia extracts with the methanolic T. chebula, T. carpenteriae and T. sericea extracts the most promising bacterial growth inhibitors, yielding MIC values as low as 200 µg mL-1 . Toxicity analyses of the extracts were favourable, and we determined that the methanolic T. chebula, T. carpenteriae and T. sericea extracts were all non-toxic. Using previously detected T. ferdinandiana antimicrobials as benchmarks, LC-MS and GC-MS fingerprint analyses revealed similar compounds in the methanolic T. chebula, T. carpenteriae and T. sericea extracts.
Conclusion:
Through these results, we propose that Terminalia spp. extracts may be useful deodorant additives to inhibit the growth of axillary and plantar malodorous bacteria, offering a biological alternative to their chemically synthesized counterparts.
... The last use, which portrays Al compounds as "helpers"-the English translation of the Latin root of adjuvantsis supposed to shock the recipient's immune defenses into action, ostensibly to enhance the immunogenicity of the pathogen(s) in the vaccine(s) [9]. Al salts are also found in dyes [10], cosmetics [5], antiperspirants [11][12][13][14], sunscreens 2 Journal of Toxicology [15,16], and thousands of material products including foils, food containers, and utensils. ...
Over the last 200 years, mining, smelting, and refining of aluminum (Al) in various forms have increasingly exposed living species to this naturally abundant metal. Because of its prevalence in the earth’s crust, prior to its recent uses it was regarded as inert and therefore harmless. However, Al is invariably toxic to living systems and has no known beneficial role in any biological systems. Humans are increasingly exposed to Al from food, water, medicinals, vaccines, and cosmetics, as well as from industrial occupational exposure. Al disrupts biological self-ordering, energy transduction, and signaling systems, thus increasing biosemiotic entropy. Beginning with the biophysics of water, disruption progresses through the macromolecules that are crucial to living processes (DNAs, RNAs, proteoglycans, and proteins). It injures cells, circuits, and subsystems and can cause catastrophic failures ending in death. Al forms toxic complexes with other elements, such as fluorine, and interacts negatively with mercury, lead, and glyphosate. Al negatively impacts the central nervous system in all species that have been studied, including humans. Because of the global impacts of Al on water dynamics and biosemiotic systems, CNS disorders in humans are sensitive indicators of the Al toxicants to which we are being exposed.
(PDF) Aluminum-induced entropy in biological systems: Implications for neurological disease. Journal of Toxicology, 2014, Article ID 491316, 27 pages, 2014. doi:10.1155/2014/491316.. Available from: https://www.researchgate.net/publication/333582751_Aluminum-induced_entropy_in_biological_systems_Implications_for_neurological_disease_Journal_of_Toxicology_2014_Article_ID_491316_27_pages_2014_doi1011552014491316 [accessed Jun 03 2019].
... Darbre, the same principle author whose 2004 publication first raised serious concern regarding paraben exposure and breast cancer risk, 5 has published numerous articles regarding many other "xenoestrogens" found to either be present in or have the potential to accumulate in normal human and cancerous human breast tissue and to show stimulatory effects at identified concentrations. These include the chemical ultraviolet filters benzophenone 1 to 3 (oxybenzone), octylmethoxycinnamate, 4-methylbenzilidenecamphor, and homosalate via different mechanisms and with variable strength of effect 66,67 ; methylsiloxanes in personal care products (hexamethylcyclotrisiloxane [D3], octamethylcyclotetrasiloxane [D4], or decamethylcyclopentasiloxane) 68 ; aluminum in diet, antacids, and deodorants [69][70][71][72][73][74][75][76] ; environment chemicals with estrogenic activity including organochlorine pesticides and polychlorinated biphenyls (including 3,4,3',4'-tetrachlorobiphenyl) 77,78 ; benzyl salicylate (fragrance and UV light absorber), benzyl benzoate (fragrance and preservative), and butylphenyl methylpropional (lilial or ptert-butyl-α-methyl hydrocinnamic aldehyde, fragrance) 79 ; phytoestrogens including resveratrol 80,81 ; metalloestrogens including aluminum, antimony, arsenite, barium, cadmium, chromium cobalt, copper, lead, mercury, nickel, selenite, tin, and vanadate 82 ; and triclosan. 83 Conversely, the same investigative center reported an inhibitory effect for breast cancer cell growth for retinoids and, specifically, retinoic acid 84,85 and tocotrienols from vitamin E. 86 These numerous potential xenoestrogenic exposural risks have been discussed in other reviews, in addition to bisphenol A, alkylphenols, and glycol ethers, and indeed all of Annex X and beyond. ...
Parabens now being formally declared as the American Contact Dermatitis Society (non)allergen of the year, the allergologic concerns regarding parabens raised during the past century are no longer a significant issue. The more recent toxicological concerns regarding parabens are more imposing, stemming from the gravity of the noncutaneous adverse health effects for which they have been scrutinized for the past 20 years. These include endocrine activity, carcinogenesis, infertility, spermatogenesis, adipogenesis, perinatal exposure impact, and nonallergologic cutaneous, psychologic, and ecologic effects. To assert that parabens are safe for use as currently used in the cosmetics, food, and pharmaceutical industries, all toxicological end points must be addressed. We seek to achieve perspective through this exercise: perspective for the professional assessing systemic risk of parabens by all routes of exposure. The data reviewed in this article strive to provide a balanced perspective for the consumer hopefully to allay concerns regarding the safety of parabens and facilitate an informed decision-making process. Based on currently available scientific information, claims that parabens are involved in the genesis or propagation of these controversial and important health problems are premature. Haste to remove parabens from consumer products could result in their substitution with alternative, less proven, and potentially unsafe alternatives, especially given the compelling data supporting the lack of significant dermal toxicity of this important group of preservatives.
... The limitations of current available treatments are that they may be inconvenient, expensive, require extensive application, and are often disconcerting due to the reoccurrence of odour after ceasing treatment [8]. Furthermore, deodorants and antiperspirants may contain antimicrobial substances; however, with the amount of antimicrobial chemicals [such as propylene glycol, triclosan, benzalkonium chloride, and metal (e.g., aluminium) salts] being added to combat these bacteria, there is a constant concern of the toxicity and potential resistance to these ingredients [9][10][11]. ...
Foot odour (bromodosis) is an embarrassing and perplexing condition mostly caused by bacteria of the Brevibacterium species. Essential oils are a credible option as an affordable treatment of odour and contribute towards antimicrobial efficacy. Therefore, this study sets out to investigate the antimicrobial activity of essential oil combinations against odour-causing bacteria. The broth microdilution method was used to investigate the antimicrobial activity of 119 essential oil combinations, and the fractional inhibitory index was calculated to determine the interactive profile. Combinations that resulted in synergy in 1 : 1 ratios were further evaluated in different concentrations, and isobolograms were plotted to determine the influence of the ratio on overall activity. Numerous combinations could be identified as having synergistic interactions against the Brevibacterium spp. and no antagonism was observed. The combination of Juniperus virginiana (juniper) and Styrax benzoin (benzoin) demonstrated synergy against all three Brevibacterium spp. tested and J. virginiana was the essential oil responsible for the majority of the synergistic interactions. The results reported here confirm the promising potential of the majority of these oils and selected combinations in treating and controlling bromodosis.
... On the contrary, it has been linked to several toxicity effects like toxicity to the nervous, skeletal, and hematopoietic system. In addition, aluminium is still under discussion to play a role in Alzheimer's disease (Flaten 2001;Campbell 2002) as well as human breast cancer (Darbre et al. 2011). Therefore, the European Food Safety Authority established in 2008 a tolerable weekly intake of 1 mg aluminium per kg bodyweight (EFSA 2008). ...
Aluminium is an omnipresent part of everyday life. It is widely used in industry and furthermore in products like cosmetics, sun creams or it can be applied for instance as aluminium foil by consumers during food preparation in households. However, over the last decades the toxicity of aluminium for humans has been heavily discussed and is still not completely clarified. Therefore, food aluminium concentrations were investigated in different untreated foodstuff as well as a possible aluminium transfer from aluminium foil to food. The results show that untreated food is not significantly contaminated. Furthermore, short time contact to aluminium foil increases the food aluminium concentration only marginal. Nevertheless, as soon as the food is in contact to aluminium foil and at the same time in contact with metals (alloys) with a higher standard electrode potential than aluminium (-1.66 V) high aluminium contaminations were observed.
... Alzheimer's disease, encephalopathy) 44 and cancer. 45 ...
... Unlike other trace elements, our human body does not require aluminium for living. Excessive exposure of body to aluminium which can be found in consumer items such as food additive, cosmetics, antiperspirants and water may lead to Alzheimer's diseases [9,10], breast cancer [11,12] and osteomalacia [13]. It also disturbed aquatic life and plant growth in the environment [14]. ...
A novel, 100% water-soluble chalcone based chemosensing receptor {1-[3-(2-Hydroxy-phenyl)-3-oxo-propenyl]-naphthalen-2-yloxy}-acetic acid, L was synthesized and characterized. The receptor L is designed based on the chelation enhanced fluorescence (CHEF) mechanism. The chemosensing properties of L were evaluated by UV–vis and fluorescence spectrometric methods. It exhibits highly selective recognition ability towards aluminum ions in water over other metal ions. The binding stoichiometry of L− Al3+ complex is 2:1 by means of Job’s plot and the detection limit is 5.66 × 10− 8 M.
... The last use, which portrays Al compounds as "helpers"the English translation of the Latin root of adjuvantsis supposed to shock the recipient's immune defenses into action, ostensibly to enhance the immunogenicity of the pathogen(s) in the vaccine(s) [9]. Al salts are also found in dyes [10], cosmetics [5], antiperspirants [11][12][13][14], sunscreens 2 Journal of Toxicology [15,16], and thousands of material products including foils, food containers, and utensils. ...
Over the last 200 years, mining, smelting, and refining of aluminum (Al) in various forms have increasingly exposed living species to this naturally abundant metal. Because of its prevalence in the earth’s crust, prior to its recent uses it was regarded as inert and therefore harmless. However, Al is invariably toxic to living systems and has no known beneficial role in any biological systems. Humans are increasingly exposed to Al from food, water, medicinals, vaccines, and cosmetics, as well as from industrial occupational exposure. Al disrupts biological self-ordering, energy transduction, and signaling systems, thus increasing biosemiotic entropy. Beginning with the biophysics of water, disruption progresses through the macromolecules that are crucial to living processes (DNAs, RNAs, proteoglycans, and proteins). It injures cells, circuits, and subsystems and can cause catastrophic failures ending in death. Al forms toxic complexes with other elements, such as fluorine, and interacts negatively with mercury, lead, and glyphosate. Al negatively impacts the central nervous system in all species that have been studied, including humans. Because of the global impacts of Al on water dynamics and biosemiotic systems, CNS disorders in humans are sensitive indicators of the Al toxicants to which we are being exposed.
... Active ingredients in most UCPs are aluminum-based compounds as aluminum chloride and aluminum chlorohydrate. Aluminum salts have been associated with oxidative stress, DNA double strand breaks, proliferation, interference in estrogen action before (Darbre, 2009;Darbre et al., 2013a;Dyrssen et al., 1987;Farasani and Darbre, 2015;Lankoff et al., 2006;Sappino et al., 2012) (Darbre et al., 2013b(Darbre et al., , 2011Exley et al., 2007;Mannello et al., 2009). Due to the genotoxic and possibly carcinogenic effect of aluminum salts, the use of UCPs may be related to breast cancer (Darbre, 2001;Jennrich and Schulte-Uebbing, 2016;Pineau et al., 2014;Rodrigues-Peres et al., 2013;Sappino et al., 2012). ...
Background:
Previous studies on breast cancer (BC), underarm cosmetic products (UCP) and aluminum salts have shown conflicting results. We conducted a 1:1 age-matched case-control study to investigate the risk for BC in relation to self-reported UCP application.
Methods:
Self-reported history of UCP use was compared between 209 female BC patients (cases) and 209 healthy controls. Aluminum concentration in breast tissue was measured in 100 cases and 52 controls. Multivariable conditional logistic regression analysis was performed to estimate odds ratios (ORs) with 95% confidence intervals (CIs), adjusting for established BC risk factors.
Findings:
Use of UCP was significantly associated with risk of BC (p=0.036). The risk for BC increased by an OR of 3.88 (95% CI 1.03-14.66) in women who reported using UCP's several times daily starting at an age earlier than 30years. Aluminum in breast tissue was found in both cases and controls and was significantly associated to self-reported UCP use (p=0.009). Median (interquartile) aluminum concentrations were significantly higher (p=0.001) in cases than in controls (5.8, 2.3-12.9 versus 3.8, 2.5-5.8nmol/g).
Interpretation:
Frequent use of UCPs may lead to an accumulation of aluminum in breast tissue. More than daily use of UCPs at younger ages may increase the risk of BC.
... Indeed, the common deodorant additive aluminium has been linked with a wide range of negative health effects including degenerative neurological conditions (e.g. Alzheimer's disease, encephalopathy) [6] and cancer [7], although the link to cancer has not been definitively proven. Studies have indicated that aluminium additives may also cause respiratory problems and cause anaphylactic shock in susceptible individuals [6]. ...
Objective:
T. ferdinandiana extracts are potent growth inhibitors of many bacterial pathogens. They may also inhibit the growth of malodour producing bacteria and thus be useful deodorant components, although this is yet to be tested.
Methods:
T. ferdinandiana fruit and leaf solvent extracts were investigated by disc diffusion and liquid dilution MIC assays against the most significant bacterial contributors to axillary and plantar malodour formation. Toxicity was determined using the Artemia franciscana nauplii bioassay. Non-targeted HPLC separation of the methanolic leaf extract, coupled to high resolution time-of-flight (TOF) mass spectroscopy was used for the identification and characterisation of individual components in the extract.
Results:
The T. ferdinandiana leaf extracts were the most potent bacterial growth inhibitors. The leaf methanolic extract was particularly potent, with low MIC values against C. jeikeium (233μg/mL), S. epidermidis (220μg/mL), P. acnes (625μg/mL) and B. linens (523μg/mL). The aqueous and ethyl acetate leaf extracts were also potent growth inhibitors of C. jeikeium and S. epidermidis (MICs <1000μg/mL). In comparison, the fruit extracts were substantially less potent antibacterial agents, although still with MIC values indicative of moderate growth inhibitory activity. All T. ferdinandiana leaf extracts were nontoxic in the Artemia fransiscana bioassay. Non-biased phytochemical analysis of the methanolic leaf extract revealed the presence of high levels of and high diversity of tannins and high levels of the flavone luteolin.
Conclusion:
The low toxicity of the T. ferdinandiana leaf extracts and their potent growth inhibition of axillary and plantar malodour producing bacteria indicate their potential as deodorant components. This article is protected by copyright. All rights reserved.
... Aluminium salts are the antiperspirant agents in underarm cosmetics that are applied onto the skin very frequently, leading to continuous dermal exposure [71][72][73][74]. Aluminium (Al) is a metalloestrogen [71,72,74], and it has neurotoxic potential [75,76]. ...
Exposure to chemicals from different sources in everyday life is widespread; one such source is the wide range of products listed under the title “cosmetics”, including the different types of popular and widely-advertised sunscreens. Women are encouraged through advertising to buy into the myth of everlasting youth, and one of the most alarming consequences is in utero exposure to chemicals. The main route of exposure is the skin, but the main endpoint of exposure is endocrine disruption. This is due to many substances in cosmetics and sunscreens that have endocrine active properties which affect reproductive health but which also have other endpoints, such as cancer. Reducing the exposure to endocrine disruptors is framed not only in the context of the reduction of health risks, but is also significant against the background and rise of ethical consumerism, and the responsibility of the cosmetics industry in this respect. Although some plants show endocrine-disrupting activity, the use of well-selected natural products might reduce the use of synthetic chemicals. Instruments dealing with this problem include life-cycle analysis, eco-design, and green labels; in combination with the committed use of environmental management systems, they contribute to “corporate social responsibility”.
In the era of modern food industry, food packaging has gained a lot of interest that helps in protecting food from environmental factors and in maintaining the integrity of food. Aluminum, being widely used material in food packaging has been used as containers, foils and pouches in packaging of hot foods, snacks and beverages. Many studies have been conducted which show that there is an increase in Aluminum content in brains of patients with Parkinson’s and Alzheimer’s diseases. It has been suspected that leaching of Aluminum content from the food packaging is one of the main reasons. Hence in this work, a biopolymer barrier has been used in reduction of Aluminum leaching into food.
Chitosan, being a biopolymer, is non-toxic and biodegradable which has film forming and antimicrobial properties can be used as a barrier in order to prevent the leaching of Aluminum into the food. Hot rice (approx. 60°C) was used as sample for the experiment. Hot rice was wrapped in Aluminum foil and chitosan coated Aluminum foil for 90 minutes. Aluminum content was detected using inductively coupled plasma- optical emission spectrometer (ICP-OES) for only rice; rice in Aluminum foil and rice in chitosan coated Aluminum foil and found to be 2.81ppm, 3.29ppm and 2.87ppm respectively. The result obtained implied that chitosan acts as a barrier thereby inferring that chitosan coated Aluminum foil can be used to reduce leaching of Aluminum to the food and hence minimise the ill effects of Aluminum intake to the body.
Axillary odor is a malodor produced by bacterial metabolism near the apocrine glands, which often causes discomfort in an individual's daily life and social interactions. A deodorant is a personal care product designed to alleviate or mask body odor. Currently, most deodorants contain antimicrobial chemicals and fragrances for odor management; however, direct application to the underarm skin can result in irritation or sensitivity. Therefore, there is a growing interest in technologies that enable disinfection and odor control without the antiperspirants or perfumes. The cold atmospheric plasma temporally generates reactive radicals that can eliminate bacteria and surrounding odors. In this study, cultured Staphylococcus hominis and Corynebacterium xerosis, the causative bacteria of axillary bromhidrosis, were killed after 90% plasma exposure for 3 min. Moreover, the electronic nose system indicated a significant reduction of approximately 51% in 3-hydroxy-3-methylhexanoic acid and approximately 34% in 3-methyl-3-sulfanylhexan-1-ol, the primary components of axillary odor, following a 5-min plasma exposure. These results support the dual function of our deodorant in eliminating bacteria and axillary odors without the chemical agents. Therefore, cold atmospheric plasma-applied deodorant devices have great potential for the treatment and management of axillary odors as a non-contact approach without chemical use in daily life.
Developing highly sensitive fluorescent probe for Al3+ and H2O detection is highly desirable, due to aluminum toxicity poses a significant threat to public health. On the other hand, the determination of water content holds immense significance in a wide range of fields such as food processing, pharmaceutical manufacturing. In this paper, a novel acylhydrazone-based fluorescent probe P was successfully synthesized and characterized for the sequential detection of Al3+ and water in alcohols. The probe P exhibited a remarkable "turn-on" response towards Al3+ by emitting yellow fluorescence at 567 nm, with high selectivity and large Stokes shift (147 nm). Meanwhile, the in situ formed P-Al3+ complex demonstrated significant solvatofluorochromic characteristic, which could be utilized as a second probe for detecting water via fluorescence quenching with low detection limit in alcohols (0.008%, methanol; 0.013%, ethanol; 0.013%, isopropanol; 0.037%, n-butanol; vol.%) and acetonitrile (0.072%, vol.%). Moreover, the P-Al3+ complex was able to detect the alcoholic strength of Chinese Baijiu without the interference of other alcohols, providing an excellent recovery rate (100.0-107.0%). Different Chinese Baijius, with various alcoholic strength, could be distinguished by simple test strips. Furthermore, the P-Al3+ complex could also analyze the water content in organic solvents .
This study demonstrated a one-pot process for the preparation of seaweed-based antibacterial foot care gel for the removal of odor. Foot gel comprised 97.5% water, 1.2% seaweed polymer, 0.2% bioactive molecule, and 1.1% preservative. The antibacterial efficiency of foot gel was tested against 14 bacterial strains, isolated from foot swab samples from five different healthy volunteers having foul foot odor. The 16S rRNA partial gene sequencing identification revealed all 14 bacterial strains were different Bacillus species. Foot gel was characterized using FTIR, Rheology, TGA, and gelling properties. The volunteer's feet were treated with just two drops (around 200 L) of foot care gel before wearing socks, which showed restriction in the growth of bacterial strains causing a foul odor within a few hours, therefore resulting in restrained the foul foot odor. Furthermore, the volunteer’s remarks about feeling freshness, coolness, dryness, and smooth feet after applying the foot gel were very encouraging. The shelf life of foot gel was monitored for up to six months and during that time, no significant change in rheological characteristics and antibacterial efficiency was observed. Foot gel was compared with commercially available foot care products and foul odor removal efficiency was found identical in both. Results of this study showed that the odor-removing efficacy of developed foot gel was found better than other commercial products.
Graphical abstract
Schematic representation of the preparation of antibacterial foot care gel and its efficacy
Several pollutants can alter neonatal prostatic development predisposing this gland to diseases. The toxicity and endocrine disrupting potential of aluminum has been reported in many organs, but little is known about its effects on the prostate. This study aimed to evaluate the effects that aluminum neonatal exposure can cause in the male ventral prostate and in the female prostate of adult and senile gerbils. Male and female pups were treated orally with aluminum chloride (10 mg/kg) from the 1st to the 14th day life. After treatment, the animals were aged until they reached 90 days or 1 year of life. The prostate glands were dissected out and submitted to morphological, immunohistochemical and ultrastructural analyses. Ventral prostates of adult males showed moderate hyperplasia and increased epithelial proliferation not associated with androgen receptor (AR) deregulation. On the other hand, senile males showed intense prostatic hyperplasia, and increased cell proliferation and epithelial AR regulation. Additionally, at both ages, there was a reduction in the prostate secretory function. The morphological changes observed in the female prostate were like those found in males. However, in adult females, prostatic hyperplasia was accompanied by a lower regulation of AR and estrogen receptor alpha, while in senile females, intense hyperplastic growth was associated with an increase in estrogen receptor alpha and a reduction in stromal AR. These results demonstrate that aluminum chloride neonatal exposure alters the hormonal regulation of the male and female prostate, inducing tissue damage that occurs in adulthood and intensifies during aging.
Rhizobacteria are versatile microbes that dwell on the rhizosphere of the plants and directly benefit the plant in the growth process. They have the unique physiological machinery through which they either produce growth-promoting substances or solubilize minerals thereby facilitating the plants to absorb them. The unique physiology of the rhizobacteria is also being exploited for a number of environment-related issues among which phytoremediation of heavy metals is most extensively investigated and studied. Pollution by heavy metals is presently a matter of concern adversely affecting public and animal health. Scientists are adapting to more sustainable and cost-effective “green technologies” for the removal of metal contaminants from polluted regions. The use of plants has proved to be extremely useful in the removal of contaminants. This involvement is further fortified by the rhizobacteria which further facilitates in the absorption of metals by the plants. The chapter highlights the various beneficial activities of rhizobacteria for the removal of metal contamination. Efforts would be given to illustrate the mechanistic aspects of the phytoremediation process.KeywordsRhizobacteriaPhytoremediationHeavy metalsCancerOxidative stress
Deodorant products forestall the development and action of the debasing apocrine organ microbes
living in the armpit. Normal antibacterial specialists in the market like triclosan and aluminum salts,
regardless of their reasonable antibacterial impacts, increment the danger of Alzheimer’s malady, bosom
and prostate malignancies or actuate contact dermatitis. Notwithstanding spreading of bacterial opposition against anti-infection agents, so one of the most significant strides in microbiological explores is
to locate another antimicrobial compound with negligible reactions. In this manner, normal antiperspirants like lemon juice having antibacterial impacts are of intrigue. The aim of the present study was to
verify the in vitro comparative antimicrobial effects of different deodorants, alum, sodium bicarbonate
and lemonjuice suspensions against two major bacteria responsible for axillary odor (Staphylococcus
epidermidis and corynebacterium) by agar well diffusion method. The results acquired explained that all
analyzed normal substances and commercial deodorants have a noteworthy antibacterial impact against
the axillary related scent bacteria with various inhibitory zone measures recommended that the natural
deodorants were much better in addition to that extracting the ingredients of commercial deodorants
with hot aqueous extract lead, to increase the significant of its antibacterial effect so it is the main advice
for the manufacturers.
This study investigated the aluminum content in one of the most consumed daily beverages: coffee. The total Al concentration in 10 different samples of coffee beans and their water-extractable fraction were determined. We then tested the influence of different brewing methods on the concentration of the extracted Al in the final beverage. Metal analyses were performed using graphite furnace atomic absorption spectroscopy (GF-AAS) after microwave-assisted acid digestion. The results showed highly variable Al contents in coffee beans (1.5−15.5 mg kg −1), of which ∼2−10% were water-extractable. The brewing technique had a major influence on the Al content in the beverage: significantly higher Al concentrations (72.57 ± 23.96 μg L −1) occurred in coffee brewed in an aluminum moka pot. Interestingly, using ground coffee with this method even reduced the Al content in the final beverage compared to the brewing water used. Coffee brewed from Al capsules did not contain significantly higher Al concentrations compared to other methods.
Backgroung
Exposure to environmental pollutants in critical developmental windows may predispose the prostate to permanent changes in its homeostasis. Thus, it is essential to know the effects that environmental toxics, such as aluminum, can cause during the development of this gland. The aim of this study was to evaluate the effects of neonatal aluminum exposure on the ventral male prostate and the female prostate of 15 days old gerbils.
Methods
Male and female gerbils were exposed orally to 10 mg/kg/day of aluminum chloride from the 1st to the 14th postnatal day life. At 15 days of life, gerbils were euthanized and their prostates were collected for biometric, morphological, morphometric, immunohistochemical and three-dimensional reconstruction analyzes.
Results
Al exposure caused a reduction in body weight in males and a significant increase in serum testosterone levels in females. Prostate branching morphogenesis was intensified in males, who had greater length, number and area of prostatic epithelial buds. Additionally, Al altered the prostate hormonal regulation of males and females, causing up regulation of the androgen receptor and estrogen receptor alpha in the female prostate, and increased immunostaining of the androgen receptor in the ventral male prostate. These changes were associated with an increased rate of epithelial and stromal cell proliferation in both sexes.
Conclusion
Together, these results indicate that Al altered the neonatal development of the prostate and that this metal acted as an endocrine disruptor in this gland.
The safety of Aluminium in cosmetic products - Submission II
Link to opinion
https://ec.europa.eu/health/sites/health/files/scientific_committees/consumer_safety/docs/sccs_o_235.pdf
WG on Cosmetic Ingredients
SCCS members: U. Bernauer, L. Bodin (Rapporteur), Q. Chaudhry, P.J. Coenraads (Chairperson), M. Dusinska, J. Ezendam, E. Gaffet, C. L. Galli, B. Granum, E. Panteri, V. Rogiers, Ch. Rousselle, M. Stepnik, T. Vanhaecke, S. Wijnhoven
SCCS external experts: A. Koutsodimou, A. Simonnard, W. Uter
Contact: SANTE-C2-SCCS@ec.europa.eu
On request from: European Commission
SCCS Number: SCCS/1613/19
Adopted on: 03-04 March 2020
________________________________________
Conclusion of the opinion:
1. In light of the new data provided, does the SCCS consider that Aluminium compounds are safe in
• Antiperspirants,
• Other cosmetic products such as lipsticks and toothpastes?
In the light of the new data provided, the SCCS considers that the use of aluminium compounds is safe at the following equivalent aluminium concentrations up to:
· 6.25% in non-spray deodorants or non-spray antiperspirants
· 10.60% in spray deodorants or spray antiperspirants
· 2.65% in toothpaste and
· 0.77 % in lipstick
2. Does the SCCS have any further scientific concerns regarding the use of Aluminium compounds in cosmetic products taking into account exposure from other sources?
The SCCS considers that the systemic exposure to aluminium via daily applications of cosmetic products does not add significantly to the systemic body burden of aluminium from other sources. Exposure to aluminium may also occur from sources other than cosmetic products, and a major source of aluminium in the population is the diet. This assessment has not taken into account the daily dietary intake of aluminium.
3. In the event that the estimated exposure to Aluminium from specific types of cosmetic products is found to be of concern, SCCS is asked to recommend safe concentration limits for the presence of Aluminium in those cosmetic products or other risk reducing measures.
/
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Keywords:
SCCS, scientific opinion, Aluminium, Regulation 1223/2009
________________________________________
Opinion to be cited as:
SCCS (Scientific Committee on Consumer Safety), Opinion on the safety of aluminium in cosmetic products, preliminary version of 30-31 October 2019, final version of 03-04 March 2020, SCCS/1613/19.
Cannabis due to its worldwide spread in human use is considered one of the most studied issue among other illicit substances. Nevertheless, according and to recent data, cannabis safety still remain unsolved and controversial. The plethora of pharmacological and toxicological effects of the smoking cannabis is due to the multiple and chaotic interactions of more than 70 cannabinoids, their metabolic and pyrolytic products, along with more than 400 structurally different natural compounds of the plant. Δ9 and its isomer Δ8-tetraydro-cannabinol are its only psychotropic constituents, while the rest cannabinoid type molecules exhibit a wide range of interesting biological activities, thus, many cannabis preparations have been used such as potential pharmacological agents in multiple sclerosis symptoms, chemotherapy nausea, glaucoma, resisted child epilepsia etc. Nevertheless, cannabis toxicity/side effects have unreasonable been underestimated. Recent findings have revealed cellular death caused and DNA damage in hippocampus by Δ9-THC, while high exposure of cannabis have disrupted mental function by decreasing central movement control, dissability of making complex activities, influenced brain development in fetus, leading to future problems concerning child personal performance/attitude, as well as negative effects on immune, genital and cardiovascular functions. Therefore, despite the cannabis state legalization in many countries as therapeutic agent is still under deep consideration, since its standardization towards culture conditions, cannabinoid content, interactions, etc, and administration under strict control of the final therapeutic product are not yet defined in full detail. Present review article, is aiming to focusing critical concerns regarding cannabis botany-phytochemistry, pharmacology-pharmacotoxicity, in relation to “medical cannabis”and synthetic analogs use for therapeutic reasons.
A novel and simple fluorescent probe, 7-methoxychromone-3-carbaldehyde-(3′4′5′-trimethoxybenzoyl) hydrazone (L), was designed and synthesized. The probe L presented outstanding “turn-on” fluorescence response towards Al³⁺ over most other competitive ions in ethanol. The detection limit of L for recognizing Al³⁺ was measured to be 2.14 × 10⁻⁷ M. According to these excellent properties, the detecting of Al³⁺ on filter papers was studied successfully. Photoinduced electron transfer (PET) process, coupled with the CN isomerisation process, is put forward to interpret the obvious fluorescence response.
In 2017, the German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the biological tolerance value (BAT value) for aluminium [ 7429‐90‐5 ]. Available publications are described in detail.
The BAT value of 60 µg aluminium/g creatinine evaluated in 2009 was based on the linear correlation between external and internal exposure. The aim of this re‐evaluation was the derivation of a health‐based BAT value considering the most sensitive critical effect of aluminium, the neurotoxicity. For this purpose, the available studies of aluminium‐exposed workers were taken into account, when the internal aluminium exposure as well as the occurrence of subclinical neurotoxic effects were determined. The effects had been measured with standardised neuropsychological test procedures. From these studies, a no observed adverse effect level (NOAEL) of 50 µg/g creatinine for the occurrence of subtle neurotoxic effects of humans was estimated. Therefore, a BAT value of 50 µg aluminium/g creatinine was evaluated. Sampling time for long‐term exposures is at the end of the shift after several shifts.
Diese Arbeit hat zum Ziel die Darstellungsform einer Stoffgeschichte sinnvoll zu standardisieren.
Im ersten Teil werden die theoretischen Grundlagen erarbeitet, wie und
warum eine Datenbank als Medium zum Einsatz kommt, wie eine Stoffgeschichte
aufgebaut ist und deren Struktur in einer Datenbank abgebildet werden kann. Im
zweiten Teil wird beispielhaft das Material Aluminium in einer Stoffgeschichte dargestellt
und aufgezeigt, welche Möglichkeiten für eine datenbankbasierte Verarbeitung
existieren.
Foot odour, known as bromodosis, is produced as a result of a combination of exocrine secretions and bacterial growth on the feet. Several commercial essential oils have demonstrated promise in inhibiting the growth of odour-causing bacteria as a novel strategy to offer relief from this dermatological problem. South Africa harbours an abundance of diverse indigenous flora which has shown favourable antimicrobial properties. As such, the potential application of natural products against bromodosis-causing Brevibacterium species with the aim of finding cosmetically appealing and promising African sourced essential oils capable of masking foot malodour was the focus of this study. The antimicrobial activity of 41 oils were investigated using the microdilution assay where the minimum inhibitory concentrations (MICs) were reported against Brevibacillus agri (ATCC 51663), Brevibacillus epidermidis (DSM 20660) and Brevibacillus linens (DSM 20425). Ninety-five percent of the oils tested displayed noteworthy activity (MIC ≤ 1.00 mg/mL) against B. agri with S. africana-caerulea demonstrating the highest activity (0.03 mg/mL) overall. Thirty-one essential oils displayed noteworthy activity (MIC ≤ 1.00 mg/mL) against B. epidermidis. Two essential oils (Plectranthus grandidentatus and Salvia africana-lutea) displayed noteworthy activity (MIC = 1.00 mg/mL) against B. linens. The major constituents for each oil was determined using gas chromatography coupled to mass spectrometry and limonene appears to be the most frequent essential oil constituent (23 of the oils). The olfactory properties of the essentials oils displaying noteworthy activity were further considered. These findings presenting interesting anti-bromodosis activity hold great potential, as not only do the selected oils have antimicrobial activity, but the pleasant aroma of these aromatic botanicals can further mask and control foot odour.
The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the biological tolerance value (BAT value) for aluminium [CAS No. 7429‐90‐5] in 2017. Available publications are described in detail.
The BAT value of 60 µg aluminium/g creatinine evaluated in 2009 was based on the linear correlation between external and internal exposure. Aim of this re‐evaluation was the derivation of a health‐based BAT value considering the most sensitive critical effect of aluminium, the neurotoxicity. For this purpose, the available studies of aluminium‐exposed workers were taken into account, when the internal aluminium exposure as well as the occurrence of subclinical neurotoxic effects were determined. The effects had been measured with standardised neuropsychological test procedures. From these studies, a no observed adverse effect level (NOAEL) of 50 µg/g creatinine for the occurrence of subtle neurotoxic effects of humans was estimated. Therefore, a BAT value of 50 µg aluminium/g creatinine was evaluated. Sampling time for long‐term exposures is at the end of the shift after several shifts.
Le système hormonal ou endocrinien est un ensemble de glandes sécrétant des hormones qui servent de messagers chimiques. Elles contrôlent les fonctions essentielles de l'organisme comme la croissance et le développement, la reproduction ainsi que la régulation du métabolisme. Depuis quelques décennies, on a découvert que des substances chimiques naturelles ou artificielles peuvent perturber les fonctions hormonales et avoir des effets délétères sur la santé humaine aussi bien à court terme qu'à long terme. Ces substances chimiques pouvant perturber le système hormonal sont regroupées sous le terme de perturbateur endocrinien. Les perturbateurs endocriniens sont aujourd'hui à l'origine d'une préoccupation grandissante. La commission européenne en recense plus de 550. Ils sont présents dans beaucoup de produits de consommation courante, dans l'environnement, l'alimentation mais aussi dans les produits de santé. On retrouve des phtalates comme excipient pour les formes gastro-résistantes de certains médicaments mais aussi pour améliorer la flexibilité des dispositifs médicaux en plastique. Les parabènes utilisés comme conservateurs sont présents dans beaucoup de produits de parapharmacie ainsi que dans bon nombre de médicaments. Le bisphénol A, classé reprotoxique de catégorie 3 par l'Union Européenne, est lui présent dans les contenants en plastique, les tickets de caisse, les produits de dentisterie... En France, il est interdit dans les contenants alimentaires destinés aux enfants de moins de trois ans et au 1er janvier 2015 il sera interdit dans tous les conditionnements destinés à être directement en contact avec des denrées alimentaires.
L'aluminium est un métal très abondant dans la nature. Pourtant, il n'est pas présentchez l'Homme de manière naturelle et ne participe à aucune fonction essentielleconnue à ce jour. Il entre dans la composition de divers produits vendus en officine,tels que les vaccins, certains médicaments oraux (anti-acides principalement), lesanti-transpirants et d'autres cosmétiques.Depuis plusieurs années, ses effets sur la santé sont au centre des préoccupations dela population, des professionnels de santé, et des scientifiques. De nombreusesétudes ont été réalisées à ce sujet.Les études indiquent que l'aluminium peut entraîner des effets indésirablesneurologiques (autisme, encéphalopathie, maladie d'Alzheimer), hématologiques(anémie) et au niveau osseux (ostéodystrophie, ostéomalacie) suite à un passagedans le sang quelle que soit sa voie d'administration. Par ailleurs, il semble êtreresponsable d'effets locaux, tels que des nodules cutanés et la myofasciite àmacrophages suite à la vaccination. D'autres effets indésirables, tels que desirritations, de l'eczéma, et des réactions allergiques sont observés lorsqu'il estprésent dans les cosmétiques.Il a été supprimé de la composition du liquide de dialyse. Cependant, il reste présentdans les autres produits étudiés malgré les efforts pour le retirer, car il y joue un rôleimportant pour leur efficacité.L'utilisation des médicaments contenant de l'aluminium peut toutefois être évitée enles remplaçant par des médicaments qui en sont dépourvus. Quant à l'usage d'antitranspirantou de cosmétique, il n'est pas une nécessité et peut sans problème êtreévité. La notion de rapport bénéfices-risques est tout de même à garder en mémoire,notamment pour les vaccins, qui restent nécessaires pour éviter certaines maladies,malgré le risque faible d'entraîner une myofasciite à macrophages.
A new approach for the development of a highly sensitive aluminium(III) ion sensor via the preconcentration of aluminium(III) ion with a self-assembled monolayer on a gold nanoparticles modified screen-printed carbon electrode and current mediation by potassium ferricyanide redox behavior during aluminium(III) ion binding has been attempted. A monolayer of mercaptosuccinic acid served as an effective complexation ligand for the preconcentration of trace aluminium; this led to an enhancement of aluminium(III) ion capture and thus improved the sensitivity of the sensor with a detection limit of down to the ppb level. Under the optimum experimental conditions, the sensor exhibited a wide linear dynamic range from 0.041 to 12.4 μM. The lower detection limit of the developed sensor was 0.037 μM (8.90 ppb) using a 10 min preconcentration time. The sensor showed excellent selectivity towards aluminium(III) ion over other interferenceions.
Aluminium chemistry is extraordinary and complex because of a large spectrum of inorganic and organometallic complexes of varying stability in solutions. Being reactive, aluminium has the potential to interact with and influence many biomolecules, biochemical pathways, cellular processes and physiological functions, thus causing high Al toxicity. It depends not only on the total Al concentration but also on the abundance of Al chemical forms, Al speciation being highly dependent on the pH and chemical environment of the solution. The oxidative potential of aluminium leads to enhanced oxidative stress, which explains part of Al toxicity mechanisms. Al is a known pro-oxidative, cytotoxic, neurotoxic, immunogenic, pro-inflammatory and mutagenic agent. Usually, organisms are not exposed to relevant levels of aluminium but long-term accumulation causes several human diseases and disturbs plant growth. In contrast to animals and humans, plants evolved specific mechanisms to cope with Al stress. We review the existing knowledge about aluminium chemical properties, bioavailability and cell responses determining Al toxicity not only in humans but also in plants. Extraordinary chemistry of Al and complexity of biological processes require complex researches to link knowledge of Al chemistry and biology of its effects in order to find the best solution to resist the aluminium toxicity.
We present a theoretical study of reflection and transmission characteristics of a microwave planar array on a thin dielectric substrate with unit cell made of two concentric rings. This array possesses high quality factor transmission resonance with polarization insensitivity for normally incident plane wave. This resonance is defined by the trapped-mode regime. We show that for oblique incidence, there are some differences in characteristics of the array and a small change in quality factor of the trapped-mode resonance.
The BJC is owned by Cancer Research UK, a charity dedicated to understanding the causes, prevention and treatment of cancer and to making sure that the best new treatments reach patients in the clinic as quickly as possible. The journal reflects these aims. It was founded more than fifty years ago and, from the start, its far-sighted mission was to encourage communication of the very best cancer research from laboratories and clinics in all countries. The breadth of its coverage, its editorial independence and it consistent high standards, have made BJC one of the world's premier general cancer journals. Its increasing popularity is reflected by a steadily rising impact factor.
The inflammatory chemokines CCL2 (MCP-1) & CCL5 (RANTES) and the inflammatory cytokines TNFα & IL-1β were shown to contribute to breast cancer development and metastasis. In this study, we wished to determine whether there are associations between these factors along stages of breast cancer progression, and to identify the possible implications of these factors to disease course.
The expression of CCL2, CCL5, TNFα and IL-1β was determined by immunohistochemistry in patients diagnosed with: (1) Benign breast disorders (=healthy individuals); (2) Ductal Carcinoma In Situ (DCIS); (3) Invasive Ducal Carcinoma without relapse (IDC-no-relapse); (4) IDC-with-relapse. Based on the results obtained, breast tumor cells were stimulated by the inflammatory cytokines, and epithelial-to-mesenchymal transition (EMT) was determined by flow cytometry, confocal analyses and adhesion, migration and invasion experiments.
CCL2, CCL5, TNFα and IL-1β were expressed at very low incidence in normal breast epithelial cells, but their incidence was significantly elevated in tumor cells of the three groups of cancer patients. Significant associations were found between CCL2 & CCL5 and TNFα & IL-1β in the tumor cells in DCIS and IDC-no-relapse patients. In the IDC-with-relapse group, the expression of CCL2 & CCL5 was accompanied by further elevated incidence of TNFα & IL-1β expression. These results suggest progression-related roles for TNFα and IL-1β in breast cancer, as indeed indicated by the following: (1) Tumors of the IDC-with-relapse group had significantly higher persistence of TNFα and IL-1β compared to tumors of DCIS or IDC-no-relapse; (2) Continuous stimulation of the tumor cells by TNFα (and to some extent IL-1β) has led to EMT in the tumor cells; (3) Combined analyses with relevant clinical parameters suggested that IL-1β acts jointly with other pro-malignancy factors to promote disease relapse.
Our findings suggest that the coordinated expression of CCL2 & CCL5 and TNFα & IL-1β may be important for disease course, and that TNFα & IL-1β may promote disease relapse. Further in vitro and in vivo studies are needed for determination of the joint powers of the four factors in breast cancer, as well as analyses of their combined targeting in breast cancer.
Elevated levels of the calcium-binding protein S100A4 promote metastasis and in carcinoma cells are associated with reduced
survival of cancer patients. S100A4 interacts with target proteins that affect a number of activities associated with metastatic
cells. However, it is not known how many of these interactions are required for S100A4-promoted metastasis, thus hampering
the design of specific inhibitors of S100A4-induced metastasis. Intracellular S100A4 exists as a homodimer through previously
identified, well conserved, predominantly hydrophobic key contacts between the subunits. Here it is shown that mutating just
one key residue, phenylalanine 72, to alanine is sufficient to reduce the metastasis-promoting activity of S100A4 to 50% that
of the wild type protein, and just 2 or 3 specific mutations reduces the metastasis-promoting activity of S100A4 to less than
20% that of the wild type protein. These mutations inhibit the self-association of S100A4 in vivo and reduce markedly the affinity of S100A4 for at least two of its protein targets, a recombinant fragment of non-muscle
myosin heavy chain isoform A, and p53. Inhibition of the self-association of S100 proteins might be a novel means of inhibiting
their metastasis-promoting activities.
Using archived tumours, those from 1984-1986 and 1996-1997 underwent immunohistochemistry for hormone receptors and grade analysis. A significant shift towards more ER-positive and low-grade disease was found; this appears to reflect screening practices, but could still influence survival.
In vitro neutron activation analysis (NAA) was performed on malignant and adjacent normal tissue from 46 human female breast tumours. The objective was to investigate the chemical environment of the tissues within which microcalcifications develop and to develop a method for discrimination between malignant and normal breast tissue. The elements Al, Br, Ca, Cl, Co, Cs, Fe, K, Mn, Na, Rb and Zn were significantly higher in the cancer tissues (all p < 0.001; except for Co, p < 0.003, Wilcoxon signed-ranks test). In addition, a significant correlation (0.80, Spearman rank correlation) was found for Rb and Zn in tumour tissues. Present results are supported by the findings of others. The relevance of elevated concentrations of these elements in cancer breast tissue remains a matter of conjecture. Evidence suggests that there is a connection both with increased cellular activity and blood supply and the formation of microcalcifications in malignant breast tissues. This study suggests an association between the elemental composition of breast tissues and the formation of breast particles. That is, elevations of elemental concentration and clustered calcifications in breast are possibly related.
The ability of aluminum to inhibit the (Na(+)/K(+))ATPase activity has been observed by several investigators. The (Na(+)/K(+))ATPase is characterized by a complex molecular heterogeneity that results from the expression and differential association of multiple isoforms of both catalytic (alpha) and regulatory (beta) subunits. For instance, three main alpha (alpha(1), alpha(2) and alpha(3)) and three beta (beta(1), beta(2) and beta(3)) subunit isoforms exist in vertebrate nervous tissue, whereas only alpha(1) and beta(1) have been identified in kidney. However, no studies have focused on determining the change in (Na(+)/K(+))ATPase isoforms caused by chronic exposure to aluminum and its relation with aluminum toxicity. In this study, adult male Wistar rats were submitted to chronic dietary AlCl(3) exposure (0.03 g/day of AlCl(3) for 4 months), and the activity and protein expression of (Na(+)/K(+))ATPase isozymes were studied in brain cortex synaptosomes and in kidney homogenates. The intracellular levels of adenine nucleotides, plasma membrane integrity, and aluminum accumulation were also studied in brain synaptosomes. Aluminum accumulation upon chronic dietary AlCl(3) administration significantly decreased the (Na(+)/K(+))ATPase activity measured in the presence of nonlimiting Mg-ATP concentrations, without compromising protein expression of alpha-subunit isoforms in brain and kidney. Aluminum-induced synaptosomal (Na(+)/K(+))ATPase inhibition was due to a reduction in the activity of isozymes containing alpha(1)-alpha(2) and alpha(3)-subunits. The onset of enzyme inhibition was accompanied by a decrease of the (Na(+)/K(+))ATPase sensitivity to submicromolar concentrations of ouabain, and it preceded major damage in plasma membrane integrity and energy supply, as revealed by the analysis of lactate dehydrogenase leakage and endogenous adenine nucleotides. The data suggest that, during chronic dietary exposure to AlCl(3), brain (Na(+)/K(+))ATPase activity drops, even if no significant alterations of catalytic subunit protein expression, cellular energy depletion, and changes in cell membrane integrity are observed. Implications regarding underlying mechanisms of aluminum neurotoxicity are discussed.
Mutations in the BRCA genes increase the risk of breast cancer. Valid estimates of the magnitude of the lifetime risk of breast cancer in BRCA gene mutation carriers are needed for genetic counseling. Recent results suggest that penetrance has increased in recent birth cohorts. We examined the cumulative breast cancer incidence and mortality before age 70 over a diagnosis period of 80 years in Icelandic women who carried the BRCA2 founder mutation 999del5.
Information on all breast cancers diagnosed in Iceland since 1911 was obtained from the Icelandic Cancer Registry. Mutation status was determined by molecular analysis of tissue samples for 847 breast cancer probands who were diagnosed from 1921 through 1985 and selected without knowledge of family history of breast cancer. We estimated the cumulative incidence and mortality from breast cancer before age 70 years in BRCA2 mutation carriers from the observed risks in first-degree relatives who were classified according to mutation status of probands and followed-up through 2002. Poisson modeling of these risks was also carried out. All statistical tests were two-sided.
Of the 847 probands, 88 carried the BRCA2 999del5 mutation and 759 did not. According to Poisson modeling, the cumulative incidence of breast cancer before age 70 years in mutation carriers increased from 18.6% (95% CI = 11.0% to 29.5%) in calendar year 1920 to 71.9% (95% CI = 45.9% to 100%) in 2002 (P < .001); in relatives of probands who did not carry the BRCA2 mutation and in the general Icelandic population incidence increased over the same period from 2.6% to 10.7% and from 1.8% to 7.5%, respectively (all increases of approximately fourfold). During the same period, the cumulative risk of death from breast cancer before age 70 years for BRCA2 mutation carriers increased from 12.1% (95% CI = 5.3% to 23.9%) to 26.9% (95% CI = 10.9% to 55.5%) (P = .08). However, because the probands were breast cancer patients and not a random sample from the population, some bias in the estimation of time trends in penetrance cannot be ruled out.
The results indicate that the penetrance of the Icelandic BRCA2 founder mutation increased nearly fourfold in 80 years, whereas the risk of death from breast cancer before age 70 years increased only approximately twofold. Changes in penetrance with time should be considered when penetrance is estimated.
S100P, an EF-hand calcium-binding protein, has been reported to be associated with the progression of many types of cancers. Transfection of an expression vector for S100P into a benign, nonmetastatic rat mammary cell line causes a 4- to 6-fold increase in its level in all four transformant cell clones. When the resultant transformant cell lines are introduced in turn into the mammary fat pads of syngeneic Furth-Wistar rats, there is a significant 3-fold increase in local muscle invasion and a significant induction of metastasis in 64% to 75% of tumor-bearing animals. In a group of 303 breast cancer patients followed for up to 20 years, antibodies to S100P immunocytochemically stain 161 primary tumors. Survival of patients with S100P-positive carcinomas is significantly worse by about 7-fold than for those with negatively stained carcinomas. There is also a significant association between the class level of immunocytochemical staining of the carcinoma cells and decreased patient survival. Positive staining for S100P is significantly associated with that for two other metastasis-inducing proteins, S100A4 and osteopontin. Patients with tumors that stained positively for both S100P and S100A4 have a significantly reduced survival of 1.1% over patients with either S100 protein alone. Multivariate regression analysis identifies S100P, S100A4, and osteopontin as the most significant independent indicators of death in this group of patients. These results suggest that stratification of patients into groups according to expression of multiple metastasis-inducing proteins may lead to a more accurate prediction of patient survival.
Aluminum (Al) is the most abundant metal and the third common chemical element on earth. It is known that Al is toxic, especially its trivalent form (Al(3+)), that represents the its most soluble form. Al intoxication is related to some pathogenic disorders, principally neurodegeneratives ones as Parkinson and Alzheimer diseases. The present study aimed to evaluate the mutagenic potential of aluminum chloride (AlCl(3)). Comet assay and chromosome aberrations analysis were applied to evaluate the DNA-damaging and clastogenic effects of AlCl(3), respectively, in different phases of the cell cycle. Cultured human lymphocytes were treated with 5, 10, 15 and 25 microM aluminum chloride during the G1, G1/S, S (pulses of 1 and 6h), and G2 phases of the cell cycle. All tested concentrations were cytotoxic and reduced significantly the mitotic index in all phases of cell cycle. They also induced DNA damage and were clastogenic in all phases of cell cycle, specially in S phase. AlCl(3) also induced endoreduplication and polyploidy in treatments performed during G1 phase. The presence of genotoxicity and polyploidy on interphase and mitosis, respectively, suggests that aluminum chloride is clastogenic and indirectly affects the construction of mitotic fuse in all tested concentrations.
Background:
Breast cancer, a complex and multifactorial disease, is the most commonly diagnosed malignancy that affects women. Methods of breast cancer detection that are available at present have well-described limitations; the intraductal approaches directly assess the microenvironment of the breast.
Objective:
The aim of this overview is to highlight the application of nipple-aspirate fluid studies in the field of biomarker discovery, useful for early detection and prevention of breast cancer risk.
Conclusion:
Nipple-aspirate fluids can be obtained non-invasively from the breast in most women and represent a promising biological tool to assess metabolic and molecular changes of cells lining the ducts from which breast cancer arises.
Breast cancer, a complex and multifactorial disease, is the most commonly diagnosed malignancy affecting women. Methods currently available for breast cancer detection have well-described limitations; in this respect, the intraductal approaches directly assess the microenvironment of the breast. Nipple aspirate fluid (NAF) can be noninvasively obtained from the breast in most women and represents a promising biological tool to assess metabolic, hormonal and molecular changes occurring in the cells lining the ducts, from which breast cancer arises. The aim of this review is to highlight the application of NAF studies in the field of biomarker discovery, which provide results useful for early detection and prevention of breast cancer risk; in fact, the analysis of NAF (mirroring the ductal-lobular microenvironment) is a reliable method for assessment of metabolic/hormonal pathways within the mammary gland, identifying biomolecular mechanisms of breast cancer initiation and progression. The intracrinology of breast microenvironment (i.e., hormonal status in NAF) may provide independent diagnostic/prognostic factors, highlighting the importance of early altered hormonal metabolism (e.g., aromatase, estrogen sulfotransferase and steroid sulfatase pathway) in relation to breast cancer initiation. The possible application of targeted therapies through the inhibition of intratumoral enzymes involved in steroid metabolism is also discussed. The intraductal approach to hormone analyses may provide a further panel of biomarkers providing clinical benefits and strengthening the armory against breast cancer.
In order to increase the chemical/thermal stability of the sulfonated poly(ether ether ketone) (sPEEK) polymer for direct methanol fuel cell (DMFC) applications at medium temperatures (up to 130ºC), novel inorganic-organic composite membranes were prepared using sPEEK polymer as organic matrix (sulfonation degree, SD, of 42 and 68%) modified with zirconium phosphate (ZrPh) pre-treated with n-propylamine and polybenzimidazole (PBI). The analyzed compositions were: 10wt.% ZrPh and 5.6wt.% PBI; 20wt.% ZrPh and 11.2wt.% PBI. These composite membranes were tested in DMFC at several temperatures by evaluating the current-voltage polarization curve, open circuit voltage (OCV) and constant voltage current (CV, 35mV). The fuel cell ohmic resistance (null phase angle impedance, NPAI) and CO2 concentration in the cathode outlet were also measured. A method is also proposed to evaluate the fuel cell Faraday and global efficiency considering the CH3OH, CO2, H2O, O2 and N2 permeation through the proton exchange membrane (PEM) and parasitic oxidation of the crossover methanol in the cathode. In order to improve the analysis of the composite membrane properties, selected characterization results presented in [V.S. Silva, B. Ruff,ann, S. Vetter, A. Mendes, L.M. Madeira, S.P. Nunes, Catal. Todaym in press] were also used in the present study. The unmodified sPEEK membrane with SD=42% (S42) was used as the reference material. In the present study, the composite membrane prepared with sPEEK SD=68% and inorganic composition of 20.0wt.%ZrPh and 11.2wt.%PBI proved to have a good relationship between proton conductivity, aqueous methanol swelling and permeability. DMFC tests results for this membrane showed similar current density output and higher open circuit voltage compared to that of sPEEK with SD=42%, but with much lower CO2 concentration in the cathode outlet (thus higher global efficiency) and higher thermal/chemical stability. This membrane was also tested at 130ºC with pure oxygen (cathode inlet) and achieved a maximum power density of 50.1 mW cm-2 at 250 mA cm-2.
Clinical studies dating back decades report a disproportionately high number of female breast cancers originating in the upper outer quadrant of the breast [1], and although this is attributed to a greater amount of epithelial tissue in that region, it is also the area to which underarm cosmetic products are applied [2,3]. Early studies reported 31% of cancers in the upper outer quadrant [1], but later studies in the 1990s report up to 61% [2,3]. The annually recorded quadrant incidence of breast cancer in Britain documents a rise in England and Wales from 47.9% in the upper outer quadrant in 1979 to 53.3% in 2000, and in Scotland a rise from 38.3% in the upper outer quadrant in 1980 to 54.7% in 2001 [4]. Any increase in the disproportionality of breast cancer in the upper outer quadrant would be inconsistent with an explanation relating to the greater amount of target epithelial tissue in that region but does parallel the increasing use of cosmetics in the underarm area [2-5].
Aluminium is not a physiological component of the breast but has been measured recently in human breast tissues and breast cyst fluids at levels above those found in blood serum or milk. Since the presence of aluminium can lead to iron dyshomeostasis, levels of aluminium and iron-binding proteins (ferritin, transferrin) were measured in nipple aspirate fluid (NAF), a fluid present in the breast duct tree and mirroring the breast microenvironment. NAFs were collected noninvasively from healthy women (NoCancer; n = 16) and breast cancer-affected women (Cancer; n = 19), and compared with levels in serum (n = 15) and milk (n = 45) from healthy subjects. The mean level of aluminium, measured by ICP-mass spectrometry, was significantly higher in Cancer NAF (268.4 ± 28.1 μg l(-1) ; n = 19) than in NoCancer NAF (131.3 ± 9.6 μg l(-1) ; n = 16; P < 0.0001). The mean level of ferritin, measured through immunoassay, was also found to be higher in Cancer NAF (280.0 ± 32.3 μg l(-1) ) than in NoCancer NAF (55.5 ± 7.2 μg l(-1) ), and furthermore, a positive correlation was found between levels of aluminium and ferritin in the Cancer NAF (correlation coefficient R = 0.94, P < 0.001). These results may suggest a role for raised levels of aluminium and modulation of proteins that regulate iron homeostasis as biomarkers for identification of women at higher risk of developing breast cancer. The reasons for the high levels of aluminium in NAF remain unknown but possibilities include either exposure to aluminium-based antiperspirant salts in the adjacent underarm area and/or preferential accumulation of aluminium by breast tissues.
The S100 gene family encode low molecular weight proteins implicated in cancer progression. In this study, we analyzed the expression of four S100 genes in one cohort of patients with breast cancer and 16 S100 genes in a second cohort. In both cohorts, the expression of S100A8 and S1009 mRNA level was elevated in high-grade compared to low-grade tumors and in estrogen receptor-negative compared to estrogen receptor-positive tumors. None of the S100 transcripts investigated were significantly associated with the presence of lymph node metastasis. Notably, multiple S100 genes, including S100A1, S100A2, S100A4, S100A6, S100A8, S100A9, S100A10, S100A11, and S100A14 were upregulated in basal-type breast cancers compared to non-basal types. Using Spearman's correlation analysis, several S100 transcripts correlated significantly with each other, the strongest correlation has been found between S100A8 and S100A9 (r = 0.889, P < 0.001, n = 295). Of the 16 S100 transcripts investigated, only S100A11 and S100A14 were significantly associated with patient outcome. Indeed, these two transcripts predicted outcome in the cohort of patients that did not receive systemic adjuvant therapy. Based on our findings, we conclude that the different S100 genes play varying roles in breast cancer progression. Specific S100 genes are potential targets for the treatment of basal-type breast cancers.
Our objective was to provide a scholarly review of the published literature on menopausal hormonal therapy (MHT), make scientifically valid assessments of the available data, and grade the level of evidence available for each clinically important endpoint. PARTICIPANTS IN DEVELOPMENT OF SCIENTIFIC STATEMENT: The 12-member Scientific Statement Task Force of The Endocrine Society selected the leader of the statement development group (R.J.S.) and suggested experts with expertise in specific areas. In conjunction with the Task Force, lead authors (n = 25) and peer reviewers (n = 14) for each specific topic were selected. All discussions regarding content and grading of evidence occurred via teleconference or electronic and written correspondence. No funding was provided to any expert or peer reviewer, and all participants volunteered their time to prepare this Scientific Statement.
Each expert conducted extensive literature searches of case control, cohort, and randomized controlled trials as well as meta-analyses, Cochrane reviews, and Position Statements from other professional societies in order to compile and evaluate available evidence. No unpublished data were used to draw conclusions from the evidence.
A consensus was reached after several iterations. Each topic was considered separately, and a consensus was achieved as to content to be included and conclusions reached between the primary author and the peer reviewer specific to that topic. In a separate iteration, the quality of evidence was judged using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system in common use by The Endocrine Society for preparing clinical guidelines. The final iteration involved responses to four levels of additional review: 1) general comments offered by each of the 25 authors; 2) comments of the individual Task Force members; 3) critiques by the reviewers of the Journal of Clinical Endocrinology & Metabolism; and 4) suggestions offered by the Council and members of The Endocrine Society. The lead author compiled each individual topic into a coherent document and finalized the content for the final Statement. The writing process was analogous to preparation of a multiauthored textbook with input from individual authors and the textbook editors.
The major conclusions related to the overall benefits and risks of MHT expressed as the number of women per 1000 taking MHT for 5 yr who would experience benefit or harm. Primary areas of benefit included relief of hot flashes and symptoms of urogenital atrophy and prevention of fractures and diabetes. Risks included venothrombotic episodes, stroke, and cholecystitis. In the subgroup of women starting MHT between ages 50 and 59 or less than 10 yr after onset of menopause, congruent trends suggested additional benefit including reduction of overall mortality and coronary artery disease. In this subgroup, estrogen plus some progestogens increased the risk of breast cancer, whereas estrogen alone did not. Beneficial effects on colorectal and endometrial cancer and harmful effects on ovarian cancer occurred but affected only a small number of women. Data from the various Women's Health Initiative studies, which involved women of average age 63, cannot be appropriately applied to calculate risks and benefits of MHT in women starting shortly after menopause. At the present time, assessments of benefit and risk in these younger women are based on lower levels of evidence.
The purpose of the study was to investigate the effect of subchronic aluminum (Al) exposure on iron (Fe) homeostasis in rats. One hundred Wistar rats were divided into two groups. Experimental rats were given drinking water containing aluminum chloride (AlCl(3), 430 mg Al(3+)·L(-1)), while control rats were given distilled water for up to 150 days. Ten rats were sacrificed in each group every 30 days. Mean corpuscular hemoglobin (MCH), and serum levels of Al, Fe, transferrin (TF), total iron binding capacity (TIBC), and soluble transferrin receptor (sTfR) were measured. Al-treated rats showed significantly decreased bodyweight and increased Al and Al/Fe levels during the experimental period. Fe levels and MCH were higher on day 150 in the experimental group than in the control group. TF content and TIBC were higher, whereas erythrocyte counts and sTfR content were lower in the experimental group than in the control group from days 90 and 60, respectively. Longer duration of Al administration increased the serum levels of Al, TF, Al/Fe, and TIBC and decreased sTfR. MCH and Fe levels decreased first, and then increased. The results indicate that chronic exposure to Al disturbed Fe homeostasis.
Unlabelled:
Many environmental compounds with oestrogenic activity are measurable in the human breast and oestrogen is a known factor in breast cancer development. Exposure to environmental oestrogens occurs through diet, household products and cosmetics, but concentrations of single compounds in breast tissue are generally lower than needed for assayable oestrogenic responses. Results presented here and elsewhere demonstrate that in combination, chemicals can give oestrogenic responses at lower concentrations, which suggests that in the breast, low doses of many compounds could sum to give a significant oestrogenic stimulus. Updated incidence figures show a continued disproportionate incidence of breast cancer in Britain in the upper outer quadrant of the breast which is also the region to which multiple cosmetic chemicals are applied.
Conclusion:
If exposure to complex mixtures of oestrogenic chemicals in consumer products is a factor in breast cancer development, then a strategy for breast cancer prevention could become possible.
If one was asked to produce a set of 'Trump Cards' based upon 'Forces of Nature Defining Life on Earth' then which card would be 'Top Trump'? I was recently chastised on the Darwin Today website for suggesting Darwin and 'natural selection' rather than, for example, Newton and 'gravity'. Although there is no denying the significance of gravity, my argument in favour of natural selection is simply that gravity is just one factor that contributes towards an outcome which ultimately is defined by natural selection. Both the beauty and the brilliance of natural selection are reflected in its omnipotence to explain the myriad observations of life and, as I will affirm herein, its explanation of the biological essentiality of aluminium and silicon is no exception.
Protein and proteomic high-throughput technologies provide the polypeptide signatures of nipple aspirate fluid (NAF), a breast secretion collected noninvasively from healthy individuals and cancer patients. As breast cancer develops from ductal-lobular epithelium, the analysis of NAF (mirroring the ductal-lobular microenvironment) is a useful tool for the analysis of metabolic pathways within the mammary gland, deepening our knowledge of the biomolecular mechanisms of breast cancer initiation and progression. The different protein expression of major NAF proteins, separated using 1D polyacrylamide gels, has proven valuable for the early detection of women with increased risk of cancer. The failure to recognize a single marker with sufficient clinical sensitivity and/or specificity has driven the identification of breast cancer multiple proteins by 2D electrophoresis. Mass spectrometry-based proteomic approaches (SELDI- and MALDI-TOF technologies) have allowed the characterization of differential NAF proteomic fingerprints between healthy individuals and breast cancer patients. The intraductal approach of protein and proteomic analyses may provide a panel of biomarkers to strengthen the armory against breast cancer.
Human S100A7 (psoriasin) is considered a marker for specific stages of breast cancer. hS100A15 is almost identical to hS100A7 and difficult to discriminate. We developed specific probes to distinguish hS100A7 and hS100A15, and demonstrate their differential distribution in normal breast tissue. Further, hS100A7 and S100A15 transcripts are elevated in ER/PR negative breast cancers, but hS100A15 protein is detected in all cancer specimens while hS100A7 protein is sporadically expressed. The differential regulation, expression and distribution of hS100A7 and hS100A15 and their reported distinct functions are compelling reasons to discriminate among these proteins in normal breast and breast cancers.
Gross cystic breast disease (GCBD) is the most common benign breast disorder, but the molecular basis of cyst formation remains to be identified. If the use of aluminium-based antiperspirant salts is involved in the etiology of gross breast cyst formation, it might be expected that aluminium would be at elevated levels in human breast cyst fluid (BCF). Aluminium was measured by ICP-MS in 48 samples of BCF, 30 samples of human blood serum and 45 samples of human breast milk at different stages of lactation (colostrum, intermediate, mature). The median level of aluminium in apocrine type I BCF (n = 27, 150 microg l(-1)) was significantly higher than in transudative type II BCF (n = 21, 32 microg l(-1); P < 0.0001). By comparison, aluminium measurements gave a median concentration of 6 microg l(-1) in human serum and 25 microg l(-1) in human breast milk, with no difference between colostrum, intermediate and mature milk. Levels of aluminium were significantly higher in both types of BCF than in human serum (P < 0.0001). However when compared with human breast milk, aluminium levels were only significantly higher in apocrine type I BCF (P < 0.0001) and not in transudative type II BCF (P = 0.152). It remains to be identified why such high levels of aluminium were found in the apocrine type I BCF and from where the aluminium originated. However, if aluminium-based antiperspirants are found to be the source and to play any causal role in development of breast cysts, then it might become possible to prevent this common breast disorder.
Hormone replacement therapy (HRT) has had a chequered history ever since its initial use to manage menopausal symptoms. It is clear that it has many other effects and here we review its impact on the risk of breast cancer. A clear risk is seen for current uses of combined oestrogen/progestagen pills, but this returns to normal shortly after treatment cessation. The role of oestrogen only replacement therapy is less clear, but most studies find a weaker, but still positive, association in current users. Recent sharp reductions in HRT use have been correlated with declines in breast cancer incidence in the USA, but not so clearly elsewhere.
7% of women in the western world develop palpable breast cysts. Studies of the relation between cysts and breast cancer have conflicting results. There are two clearly defined types of cyst. We investigated whether one cyst type is associated with a higher rate of breast-cancer development than the other.
We studied 1374 women with palpable breast cysts presenting between 1981 and 1987, who had cysts aspirated between 1981 and 1989. Cysts were classified as type I if the sodium/potassium (Na+/K+) ratio in the cyst fluid was less than 3, or type II if the Na+/K+ ratio was 3 or more. Data on incidence of breast cancer were available until January, 1995, and we compared them with the expected numbers of cancers calculated from age-specific breast-cancer incidence in Scotland in 1988.
65 cancers developed during follow-up. The overall standardised incidence rate of breast cancer in patients with palpable cysts was 2.81 (95% CI 2.17-3.59). The relative incidence rate was increased for all cyst types. The standardised incidence rate of developing breast cancer among women younger than 45 years was highest at 5.94 (2.97-10.63), with a significant trend for decreasing relative incidence rate with age (p<0.05). Women older than 54 years had a standardised incidence rate of 1.73 (0.86-3.10). The standardised incidence rate of breast cancer was highest in the first year after aspiration (7.02 [3.73-12.00]) but the risk was still raised after 5 years (2.68 [1.84-3.76]).
Women with breast cysts are at an increased risk of breast cancer, especially at younger ages. The type of cyst did not alter the associated relative incidence rate of breast-cancer development.
Aluminium chlorohydrate (ACH), the active ingredient in many antiperspirants, was labeled with the radioisotope 26Al. The labeled ACH was then fractionated into about 100 samples using gel filtration chromatography. Each fraction was analyzed for 26Al and total aluminium content. Aluminium-26 was only detected in the fractions that also contained aluminium, which verified that the ACH was uniformly labeled. 84 mg of the labeled ACH was then applied to a single underarm of two adult subjects with blood and urine samples being collected over 7 weeks. Tape-stripping and mild washings of the skin were also collected for the first 6 days. Results indicate that only 0.012% of the applied aluminium was absorbed through the skin. At this rate, about 4 microg of aluminium is absorbed from a single use of ACH on both underarms. This is about 2.5% of the aluminium typically absorbed by the gut from food over the same time period. Therefore, a one-time use of ACH applied to the skin is not a significant contribution to the body burden of aluminium.
Breast cancer is the commonest cause of cancer death in women worldwide. Rates vary about five-fold around the world, but they are increasing in regions that until recently had low rates of the disease. Many of the established risk factors are linked to oestrogens. Risk is increased by early menarche, late menopause, and obesity in postmenopausal women, and prospective studies have shown that high concentrations of endogenous oestradiol are associated with an increase in risk. Childbearing reduces risk, with greater protection for early first birth and a larger number of births; breastfeeding probably has a protective effect. Both oral contraceptives and hormonal therapy for menopause cause a small increase in breast-cancer risk, which appears to diminish once use stops. Alcohol increases risk, whereas physical activity is probably protective. Mutations in certain genes greatly increase breast-cancer risk, but these account for a minority of cases.
Breast cancer incidence suggests a lifestyle cause. A lifestyle factor used near the breast is the application of antiperspirants/deodorants accompanied by axillary shaving. A previous study did not support a link with breast cancer. If these habits have a role in breast cancer development, women using antiperspirants/deodorants and shaving their underarms frequently would be expected to have an earlier age of diagnosis than those doing so less often. An earlier age of diagnosis would also be expected in those starting to use deodorants and shaving at an earlier age. This is the first study to investigate the intensity of underarm exposure in a cohort of breast cancer survivors. Four hundred and thirty-seven females diagnosed with breast cancer were surveyed. Once grouped by their frequency of underarm hygiene habits, the mean age of diagnosis was the primary end point. Secondary end points included the overall frequency of these habits, and potential usage group confounding variables were evaluated. All statistical tests were two-sided. Frequency and earlier onset of antiperspirant/deodorant usage with underarm shaving were associated with an earlier age of breast cancer diagnosis. Combined habits are likely for this earlier age of diagnosis. In conclusion, underarm shaving with antiperspirant/deodorant use may play a role in breast cancer. It is not clear which of these components are involved. Reviewed literature insinuates absorption of aluminium salts facilitated by dermal barrier disruption. Case-controlled investigations are needed before alternative underarm hygiene habits are suggested.
Although risk factors are known to include the loss of function of the susceptibility genes BRCA1/BRCA2 and lifetime exposure to oestrogen, the main causative agents in breast cancer remain unaccounted for. It has been suggested recently that underarm cosmetics might be a cause of breast cancer, because these cosmetics contain a variety of chemicals that are applied frequently to an area directly adjacent to the breast. The strongest supporting evidence comes from unexplained clinical observations showing a disproportionately high incidence of breast cancer in the upper outer quadrant of the breast, just the local area to which these cosmetics are applied. A biological basis for breast carcinogenesis could result from the ability of the various constituent chemicals to bind to DNA and to promote growth of the damaged cells. Multidisciplinary research is now needed to study the effect of long-term use of the constituent chemicals of underarm cosmetics, because if there proves to be any link between these cosmetics and breast cancer then there might be options for the prevention of breast cancer.
In the decade that has elapsed since the suggestion that exposure of the foetal/developing male to environmental oestrogens could be the cause of subsequent reproductive and developmental effects in men, there has been little definitive research to provide conclusions to the hypothesis. Issues of exposure and low potency of environmental oestrogens may have reduced concerns. However, the hypothesis that chemicals applied in body care cosmetics (including moisturizers, creams, sprays or lotions applied to axilla or chest or breast areas) may be affecting breast cancer incidence in women presents a different case scenario, not least in the consideration of the exposure issues. The specific cosmetic type is not relevant but the chemical ingredients in the formulations and the application to the skin is important. The most common group of body care cosmetic formulation excipients, namely p-hydroxybenzoic acid esters or parabens, have been shown recently to be oestrogenic in vitro and in vivo and now have been detected in human breast tumour tissue, indicating absorption (route and causal associations have yet to be confirmed). The hypothesis for a link between oestrogenic ingredients in underarm and body care cosmetics and breast cancer is forwarded and reviewed here in terms of: data on exposure to body care cosmetics and parabens, including dermal absorption; paraben oestrogenicity; the role of oestrogen in breast cancer; detection of parabens in breast tumours; recent epidemiology studies of underarm cosmetics use and breast cancer; the toxicology database; the current regulatory status of parabens and regulatory toxicology data uncertainties. Notwithstanding the major public health issue of the causes of the rising incidence of breast cancer in women, this call for further research may provide the first evidence that environmental factors may be adversely affecting human health by endocrine disruption, because exposure to oestrogenic chemicals through application of body care products (unlike diffuse environmental chemical exposures) should be amenable to evaluation, quantification and control. The exposure issues are clear and the exposed population is large, and these factors should provide the necessary impetus to investigate this potential issue of public health.
The S100 gene family comprises more than 20 members whose protein sequences encompass at least one EF-hand Ca2+ binding motif. The expression of individual family members is not ubiquitous for all tissues and there appears to be an element of tissue-specific expression. Molecular analysis of breast tumors has revealed that several S100s, including S100A2, S100A4 and S100A7, exhibit altered expression levels during breast tumorigenesis and/or progression. Subsequent studies have started to describe a functional role for these S100 proteins as well as their mechanism of action and the biochemical pathways they modify. The present review outlines what is known about S100A7 in breast cancer and summarizes the need to better understand the importance of this protein in breast cancer.
The S100A7 (psoriasin) gene is highly expressed in ductal carcinoma in situ (DCIS) of the breast and can be downregulated in invasive carcinoma. Persistent S100A7 expression in invasive carcinoma is associated with a worse prognosis, and this effect may be mediated in part through interaction with the multifunctional cell signaling protein Jab1.
In order to investigate the relationship between S100A7 and progression from DCIS to invasive carcinoma, we studied S100A7 expression in 136 patients with DCIS (including 46 patients with associated invasive carcinoma) by immunohistochemistry.
S100A7 expression was present in 63 out of 136 (46%) of DCIS lesions and was associated with estrogen receptor negative status (P = 0.0002), higher nuclear grade (P < 0.0001), necrosis (P < 0.0001) and inflammation (P < 0.0001). S100A7 status was no different between DCIS with and DCIS without an invasive component, but higher levels of S100A7 were present in DCIS associated with invasive carcinoma (P < 0.004). Analysis of a subset of cases showed that S100A7 expression was also associated with an increase in nuclear Jab1 (n = 43; P = 0.0019) and reduced p27kip1 (n = 47; P = 0.0168). In cases of DCIS associated with invasive carcinoma, there was also a significant reduction in S100A7 between in situ and invasive components (n = 46; P < 0.0001). In pure DCIS cases treated by local excision, there was no difference in frequency of S100A7 expression between patients with recurrence of DCIS (n = 9) and those without (n = 36).
The findings reported here suggest that, although S100A7 may not be a marker for recurrence of DCIS, it is associated with poor prognostic markers in DCIS and may influence progression of breast carcinoma through its interaction with and influence on Jab1.
Theory holds that the upper outer quadrant of the breast develops more malignancies because of increased tissue volume. This study evaluated genomic patterns of loss of heterozygosity (LOH) and allelic imbalance (AI) in non-neoplastic tissues from quadrants of diseased breasts following mastectomy to characterize relationships between genomic instability and the propensity for tumor development.
Tissues from breast quadrants were collected from 21 patients with various stages of breast carcinoma. DNA was isolated from non-neoplastic tissues using standard methods and 26 chromosomal regions commonly deleted in breast cancer were examined to assess genomic instability.
Genomic instability was observed in breast quadrants from patients with ductal carcinomas in situ and advanced carcinomas. Levels of instability by quadrant were not predictive of primary tumor location (P =.363), but outer quadrants demonstrated significantly higher levels of genomic instability than did inner quadrants (P =.017). Marker D8S511 on chromosome 8p22-21.3, one of the most frequently altered chromosomal regions in breast cancer, showed a significantly higher level of instability (P =.039) in outer compared with inner quadrants.
Non-neoplastic breast tissues often harbor genetic changes that can be important to understanding the local breast environment within which cancer develops. Greater genomic instability in outer quadrants can partially explain the propensity for breast cancers to develop there, rather than simple volume-related concepts. Patterns of field cancerization in the breast appear to be complex and are not a simple function of distance from a developing tumor.
BRCA1 (BReast-CAncer susceptibility gene 1) and BRCA2 are tumor suppressor genes, the mutant phenotypes of which predispose to breast and ovarian cancers. Intensive research has shown that BRCA proteins are involved in a multitude of pivotal cellular processes. In particular, both genes contribute to DNA repair and transcriptional regulation in response to DNA damage. Recent studies suggest that BRCA proteins are required for maintenance of chromosomal stability, thereby protecting the genome from damage. New data also show that BRCAs transcriptionally regulate some genes involved in DNA repair, the cell cycle, and apoptosis. Many of these functions are mediated by a large number of cellular proteins that interact with BRCAs. The functions of BRCA proteins are also linked to distinct and specific phosphorylation events; however, the extent to which phosphorylation-activated molecular pathways contribute to tumor suppressor activity remains unclear. Finally, the reasons why mutations in BRCA genes lead to the development of breast and ovarian cancers are not clearly understood. Elucidation of the precise molecular functions of BRCAs is expected to improve our understanding of hereditary as well as sporadic mammary carcinogenesis.
Breast cancer is an important contributor to morbidity and mortality in society, but factors that affect the cause of the disease are poorly defined. Genomic instability drives tumorigenic processes in invasive carcinomas and premalignant breast lesions, and might promote the accumulation of genetic alterations in apparently normal tissues before histological abnormalities are detectable. Evidence suggests that genomic changes in breast parenchyma affect the behaviour of epithelial cells, and ultimately might affect tumour growth and progression. Inherent instability in genes that maintain genomic integrity, as well as exogenous chemicals and environmental pollutants, have been implicated in breast-cancer development. Although molecular mechanisms of tumorigenesis are unclear at present, carcinogenic agents could contribute to fields of genomic instability localised to specific areas of the breast. Understanding the functional importance of genomic instability in early carcinogenesis has important implications for improvement of diagnostic and treatment strategies.
Although aluminum (Al) is responsible for the etiology of some human diseases, not much is known about the mechanisms of its genotoxic activity. The available data suggest that Al can induce DNA damage by modifying the structure of chromatin through the induction of reactive oxygen species or by damaging lysosomal membranes and liberating DNase. We treated human peripheral-blood lymphocytes with AlCl3 in the G0/G1 phase, in the S/G2 phase, and during the whole cell cycle. The aim of the study was to check if the sensitivity of lymphocytes to Al varied through the cell cycle. A high sensitivity in the S phase would point toward chromatin modification as the major source of DNA damage. Micronuclei (Mn) and apoptosis were assessed as the end points. Cells were treated with 1, 2, 5, 10, and 25 microg/mL AlCl3. Mn induced by 5 microg/mL of AlCl3 were analyzed by FISH for centromeric signal content. After all treatment schemes the frequency of Mn increased initially, but decreased at high AlCl3 concentrations. This drop of Mn frequency could be explained by a strong increase in the frequency of apoptosis. AlCl3 induced both Mn with and without centromeres. The G0/G1 phase of the cell cycle was found to be more sensitive than were the S and G2 phases. This points toward oxidative stress or liberation of DNase as the major source of DNA damage induced by Al.
Aluminium salts are used as the active antiperspirant agent in underarm cosmetics, but the effects of widespread, long term and increasing use remain unknown, especially in relation to the breast, which is a local area of application. Clinical studies showing a disproportionately high incidence of breast cancer in the upper outer quadrant of the breast together with reports of genomic instability in outer quadrants of the breast provide supporting evidence for a role for locally applied cosmetic chemicals in the development of breast cancer. Aluminium is known to have a genotoxic profile, capable of causing both DNA alterations and epigenetic effects, and this would be consistent with a potential role in breast cancer if such effects occurred in breast cells. Oestrogen is a well established influence in breast cancer and its action, dependent on intracellular receptors which function as ligand-activated zinc finger transcription factors, suggests one possible point of interference from aluminium. Results reported here demonstrate that aluminium in the form of aluminium chloride or aluminium chlorhydrate can interfere with the function of oestrogen receptors of MCF7 human breast cancer cells both in terms of ligand binding and in terms of oestrogen-regulated reporter gene expression. This adds aluminium to the increasing list of metals capable of interfering with oestrogen action and termed metalloestrogens. Further studies are now needed to identify the molecular basis of this action, the longer term effects of aluminium exposure and whether aluminium can cause aberrations to other signalling pathways in breast cells. Given the wide exposure of the human population to antiperspirants, it will be important to establish dermal absorption in the local area of the breast and whether long term low level absorption could play a role in the increasing incidence of breast cancer.
The upper outer quadrant (UOQ) of the breast is the most frequent site for incidence of breast cancer, but the reported disproportionate incidence in this quadrant appears to rise with year of publication.
In order to determine whether this increasing incidence in the UOQ is an artifact of different study populations or is chronological, data have been analysed for annual quadrant incidence of female breast cancer recorded nationally in England and Wales between 1979 and 2000 and in Scotland between 1980 and 2001.
In England and Wales, the recorded incidence of female breast cancer in the UOQ rose from 47.9% in 1979 to 53.3% in 2000, and has done so linearly over time with a correlation coefficient R of +0.71 +/- SD 0.01 (p < 0.001). Analysis of independent data from Scotland showed a similar trend in that recorded female breast cancer had also increased in the UOQ from 38.3% in 1980 to 54.7% in 2001, with a correlation coefficient R for the linear annual increase of +0.80 +/- SD 0.03 (p < 0.001).
These results are inconsistent with current views that the high level of UOQ breast cancer is due solely to a greater amount of target epithelial tissue in that region. Identification of the reasons for such a disproportionate site-specific increase could provide clues as to causative factors in breast cancer.
Although it is known that many metals induce DNA damage and inhibit DNA repair, information regarding aluminium (Al) is scarce. The aim of this study was to analyze the level of DNA damage in human peripheral blood lymphocytes treated with Al and the impact of Al on the repair of DNA damage induced by ionizing radiation. Cells were treated with different doses of aluminium chloride (1, 2, 5, 10 and 25 microg/ml AlCl(3)) for 72 h. The level of DNA damage and of apoptosis was determined by the comet assay. The level of oxidative damage was determined by the application of endonuclease III and formamidopyrimidine DNA glycosylase. The results on apoptosis were confirmed by flow cytometry. Based on the fluorescence intensity, cells were divided into cohorts of different relative DNA content that corresponds to G(1), S and G(2) phases of the cell cycle. Our results revealed that Al induces DNA damage in a dose-dependent manner, however, at the dose of 25 microg/ml the level of damage declined. This decline was accompanied by a high level of apoptosis indicating selective elimination of damaged cells. Cells pre-treated with Al showed a decreased repair capacity indicating that Al inhibits DNA repair. The possible mechanisms by which Al induces DNA damage and inhibits the repair are discussed.
For more than one and a half century the cystic disease of the breast has been recognized as the most frequent female benign breast lesion. Although some conundrums and controversies exist about the relation between gross cysts and breast cancer, recent evidence suggests that the multidisciplinary study of gross cystic breast disease (GCBD) may be a powerful tool for predicting the natural history of the multifaceted gross cyst pathology. A lot of papers have been published on breast cyst fluids (BCF) concerning biochemical, hormonal and morphological aspects, demonstrating that the intracystic fluid contains a wide variety of components (such as ions, lipids, proteins, enzymes, growth factors and antigens) and suggesting that their profile provides additional knowledge on both physiopathology and etiologic pathways of human gross cystic breast disease. The aim of this overview is the critical evaluation of all data accumulated in the last thirty years, in order to highlight the utility of biochemical and epidemiological studies to identify gross cysts, if any, at higher breast cancer risk.
Many compounds in the environment have been shown capable of binding to cellular oestrogen receptors and then mimicking the actions of physiological oestrogens. The widespread origin and diversity in chemical structure of these environmental oestrogens is extensive but to date such compounds have been organic and in particular phenolic or carbon ring structures of varying structural complexity. Recent reports of the ability of certain metal ions to also bind to oestrogen receptors and to give rise to oestrogen agonist responses in vitro and in vivo has resulted in the realisation that environmental oestrogens can also be inorganic and such xenoestrogens have been termed metalloestrogens. This report highlights studies which show metalloestrogens to include aluminium, antimony, arsenite, barium, cadmium, chromium (Cr(II)), cobalt, copper, lead, mercury, nickel, selenite, tin and vanadate. The potential for these metal ions to add to the burden of aberrant oestrogen signalling within the human breast is discussed.
The established role of oestrogen in the development and progression of breast cancer raises questions concerning a potential contribution from the many chemicals in the environment which can enter the human breast and which have oestrogenic activity. A range of organochlorine pesticides and polychlorinated biphenyls possess oestrogen-mimicking properties and have been measured in human breast adipose tissue and in human milk. These enter the breast from varied environmental contamination of food, water and air, and due to their lipophilic properties can accumulate in breast fat. However, it is emerging that the breast is also exposed to a range of oestrogenic chemicals applied as cosmetics to the underarm and breast area. These cosmetics are left on the skin in the appropriate area, allowing a more direct dermal absorption route for breast exposure to oestrogenic chemicals and allowing absorbed chemicals to escape systemic metabolism. This review considers evidence in support of a functional role for the combined interactions of cosmetic chemicals with environmental oestrogens, pharmacological oestrogens, phyto-oestrogens and physiological oestrogens in the rising incidence of breast cancer.
Since the alkyl esters of p-hydroxybenzoic acid (parabens) can be measured intact in the human breast and possess oestrogenic properties, it has been suggested that they could contribute to an aberrant burden of oestrogen signalling in the human breast and so play a role in the rising incidence of breast cancer. However, although parabens have been shown to regulate a few single genes (reporter genes, pS2, progesterone receptor) in a manner similar to that of 17beta-oestradiol, the question remains as to the full extent of the similarity in the overall gene profile induced in response to parabens compared with 17beta-oestradiol. The GE-Amersham CodeLink 20 K human expression microarray system was used to profile the expression of 19881 genes in MCF7 human breast cancer cells following a 7-day exposure to 5 x 10(-4) M methylparaben, 10(-5) M n-butylparaben and 10(-8) M 17beta-oestradiol. At these concentrations, the parabens gave growth responses in MCF7 cells of similar magnitude to 17beta-oestradiol. The study identified genes which are upregulated or downregulated to a similar extent by methylparaben, n-butylparaben and 17beta-oestradiol. However, the majority of genes were not regulated in the same way by all three treatments. Some genes responded differently to parabens from 17beta-oestradiol, and furthermore, differences in expression of some genes could be detected even between the two individual parabens. Therefore, although parabens possess oestrogenic properties, their mimicry in terms of global gene expression patterns is not perfect and differences in gene expression profiles could result in consequences to the cells that are not identical to those following exposure to 17beta-oestradiol.