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Aluminium and breast cancer: Sources of exposure, tissue measurements and mechanisms of toxicological actions on breast biology
... 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]. ...
... 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]. Furthermore, a recent in vitro study demonstrated that Al can inhibit human acetylcholinesterase, an enzyme participating in cholinergic neurotransmission [77]. ...
... There is also evidence of the ability of Al to cause problems to the osseous system, bone pain and fatigue [75,80]. Aluminium has been detected in both normal breast tissue and malignant lesions [81,82], and there are studies that suggest that the long-term use of aluminiumbased cosmetics applied topically near the breasts may be a risk factor in the etiopathology of breast cancer [71,74]. ...
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”.
... The average total daily dietary intake of aluminum is a few mg/day [1]. Direct contact with Al is also present during food processing, packaging, and storing (such as kitchen foil, vessels, and various food additives), as well as during dermal applications of personal-care products [2][3][4]. Human exposure to Al is also rising because of acid rains, which cause the partial dissolution of soil aluminum, and because of the presence of Al in tap and drinking waters due to the flocculants used in water treatment plants [5]. ...
... Various computer software can provide necessary information for calculations of Al species in terms of pH, ionic strength of solution, and temperature. Well-known models have been developed for speciation of aluminum, e.g., MINEQL, WHAM, ALCHEM and GEOCHEM, SOLMI, NEQ88, MINTE, KRIMAT, and SIMPLISIMA [4,[23][24][25][26]. ...
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.
... These factors explain only a small part of the etiology (Turnbull and Rahman, 2008) suggesting that environmental factors may also be relevant in the development of breast cancer (Bonefeld-Jorgensen et al., 2011;Coyle, 2004). A change in the topological distribution of mammary carcinoma since 1975 (Bright et al., 2016;Darbre, 2016Darbre, , 2009Darbre, , 2005Darbre, , 2003 towards an higher incidence in the upper outer quadrant seems to point to underarm cosmetic products (UCPs) as a potential contributor (Darbre, 2009(Darbre, , 2005(Darbre, , 2003Darbre et al., 2013b). Previous studies investigating the effect of UCPs on breast cancer have shown conflicting results (McGrath, 2003;Mirick et al., 2002;Pasha et al., 2008;Rodrigues-Peres et al., 2013). ...
... Mandriota et al. (2016a) demonstrated in an established cancer mouse model that concentrations of aluminum in the range of those measured in human breast are able to transform cultured mammary epithelial cells, enabling them to form tumors and to metastasize. It was further suggested that frequent use of UCPs containing aluminum salts is a main source of measured aluminum in breast structures (Darbre et al., 2013b(Darbre et al., , 2011Exley et al., 2007;Mannello et al., 2009). Due to the genotoxic and possibly EBioMedicine xxx (2017) 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.
... 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.
... Over time this leads to a high local aluminium concentration and increases the risk of breast cancer [12]. Thus it is also no surprise that higher aluminium concentrations have been measured in human breast tissue than in the blood serum [13]. Cell cultures provide some indication of the changes, which aluminium causes to healthy and diseased breast tissue cells. ...
... They cause an intracellular accumulation of iron. The associated increased formation of reactive oxygen species (ROS) causes nerve cell death [16] and is viewed as an additional risk factor for the damaging of healthy breast tissue cells [13]. If the aluminium concentration increases in the event of chronic exposure in the mitochondria, this leads to changes damaging for the entire cell metabolism [17]. ...
Breast cancer is the most common cancer among women in the Western world. In 90 [%] of breast cancers environmental factors are among the causes. The frequency with which the tumor arises in the outer upper part of the chest is increased above average in recent decades. Aluminum salts as part of deodorants and antiperspirants are absorbed from the body to a greater extent than previously thought. Their toxicity to healthy and diseased breast tissue includes several well-documented pathological mechanisms. In terms of primary and secondary prevention the potentially carcinogenic potential of aluminum and its use in antiperspirant deodorants must be reassessed. For the same reason, access to a targeted diagnosis and therapy of aluminum loads must be facilitated.
... However, the method by which alum modifies the immune system has not been fully understood. It is shown to induce a strong T H 2 immune response (9,11) and is also linked to serious autoimmune outcomes and adverse effects including association with breast cancer induction (12,13). ...
We tested how adjuvants effect in a cancer vaccine model using an epitope derived from an autoactivation loop of membrane-type protease serine protease 14 (PRSS14; loop metavaccine) in mouse mammary tumor virus (MMTV)-polyoma middle tumor-antigen (PyMT) system and in 2 other orthotopic mouse systems. Earlier, we reported that loop metavaccine effectively prevented progression and metastasis regardless of adjuvant types and TH types of hosts in tail-vein injection systems. However, the loop metavaccine with Freund's complete adjuvant (CFA) reduced cancer progression and metastasis while that with alum, to our surprise, were adversely affected in 3 tumor bearing mouse models. The amounts of loop peptide specific antibodies inversely correlated with tumor burden and metastasis, meanwhile both TH1 and TH2 isotypes were present regardless of host type and adjuvant. Tumor infiltrating myeloid cells such as eosinophil, monocyte, and neutrophil were asymmetrically distributed among 2 adjuvant groups with loop metavaccine. Systemic expression profiling using the lymph nodes of the differentially immunized MMTV-PyMT mouse revealed that adjuvant types, as well as loop metavaccine can change the immune signatures. Specifically, loop metavaccine itself induces TH2 and TH17 responses but reduces TH1 and Treg responses regardless of adjuvant type, whereas CFA but not alum increased follicular TH response. Among the myeloid signatures, eosinophil was most distinct between CFA and alum. Survival analysis of breast cancer patients showed that eosinophil chemokines can be useful prognostic factors in PRSS14 positive patients. Based on these observations, we concluded that multiple immune parameters are to be considered when applying a vaccine strategy to cancer patients.
... Accumulating evidence from in vitro and in vivo experimental studies, as well as epidemiological observations, demonstrate that increased exposures to Al can lead to a number of adverse health effects [3]. Al has been postulated to induce oxidative stress in various cell types [4,5], interfere with estrogen receptors [6], support osteomalacia via phosphate deficiency, impair calcium uptake and engender dysfunctional osteoblast proliferation [7], as well as to alter iron homeostasis by disrupting intestinal Fe absorption and normal tissue ferritin levels [8]. Of highest concern is that studies on Al uptake have revealed a neurotoxic action that is potentially implicated in different neurodegenerative disorders, including encephalopathy, Alzheimer's disease and multiple sclerosis [9][10][11]. ...
Introduction: Alcohol overuse may be related to increased aluminum (Al) exposure, the brain accumulation of which contributes to dementia. However, some reports indicate that silicon (Si) may have a protective role over Al-induced toxicity. Still, no study has ever explored the brain content of Al and Si in alcoholic use disorder (AUD). Materials and methods: To fill this gap, the present study employed inductively coupled plasma optical emission spectrometry to investigate levels of Al and Si in 10 brain regions and in the liver of AUD patients (n = 31) and control (n = 32) post-mortem. Results: Al content was detected only in AUD patients at mean ± SD total brain content of 1.59 ± 1.19 mg/kg, with the highest levels in the thalamus (4.05 ± 12.7 mg/kg, FTH), inferior longitudinal fasciculus (3.48 ± 9.67 mg/kg, ILF), insula (2.41 ± 4.10 mg/kg) and superior longitudinal fasciculus (1.08 ± 2.30 mg/kg). Si content displayed no difference between AUD and control, except for FTH. Positive inter-region correlations between the content of both elements were identified in the cingulate cortex, hippocampus, and ILF. Conclusions: The findings of this study suggest that AUD patients may potentially be prone to Al-induced neurodegeneration in their brain-although this hypothesis requires further exploration.
... 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.
... During the last decade there has been an ongoing debate about a potential association between the use of underarm cosmetics such as aluminium-based antiperspirants and breast cancer development (Mannello et al., 2011;Darbre et al., 2013). Although this hypothesis has not gained wide acceptance, it still incites vivid public discussions. ...
In the present study genotoxic effects after combined exposure of human breast cell lines (MCF-10A, MCF-7 and MDB-MB-231) to silver nanoparticles (AgNP, citrate stabilized, 15 and 45nm by STEM, Ag15 and Ag45, respectively) with aluminium chloride, butylparaben, or di-n-butylphthalate were studied. In MCF-10A cells exposed for 24h to Ag15 at the concentration of 23.5μg/mL a statistically significant increase in DNA damage in comet assay (SSB) was observed. In the presence of the test chemicals the genotoxic effect was decreased to a level comparable to control values. In MCF-7 cells a significant increase in SSB level was observed after exposure to Ag15 at 16.3μg/mL. The effect was also diminished in the presence of the 3 test chemicals. In MDA-MB-231 cells no significant increase in SSB was observed, however increased level of oxidative DNA damage (incubation with Fpg enzyme) was observed after exposure to combinations of both AgNP with aluminium chloride. No increase in micronuclei formation was observed in neither cell line after the single nor combined treatments. Our results point to a low risk of increased genotoxic effects of AgNP when used in combination with aluminium salts, butylparaben or di-n-butylphthalate in consumer products.
... However, the results of Lorenzo et al. [25] study showed that the fat concentrate and lactose contribute to the high aluminum content of milk. In another study [26], it was also shown that the levels of aluminum are generally 50-fold higher in breast milk than in blood serum which suggests that breast milk is a sink for aluminum in the body [27]. ...
The present cross-sectional study is aimed at analyzing the breast milk of lactating mothers in Hamadan, Iran for aluminum and several minerals and trace elements. Ten governmental health care centers were utilized to facilitate collection of breast milk samples. The breast milk samples were collected at 1, 2, 6, 7, and 12 months postpartum from one hundred healthy lactating women, who delivered full-term newborns. Detection of sodium (Na), zinc (Zn), calcium (Ca), iron (Fe), copper (Cu), magnesium (Mg) and aluminum (Al) levels was conducted with the use of Inductively Coupled Plasma Mass Spectrometry (ICP-MS). This method has shown high accuracy, precision, sensitivity, and linearity for the wide range of concentrations. The accumulated data were not normally distributed; thus, the non-parametric Mann-Whitney U test was used in the statistical analysis of the results. Mean concentrations of Fe, Zn, Cu, Ca, Mg, and Na were 0.75, 1.38, 0.35, 255, 34.58, and 155.72 μg/mL, respectively. The mean level of Al, a well-known neurotoxic metal, was determined to be an alarming 0.191 μg/mL. Moreover, 95% of participants contained very harmful concentrations of Al in their milk. This study also revealed Zn deficiency in about 50% of milk samples. Further investigation is needed to elucidate sources of exposure and factors that may influence maternal and fetal exposure to aluminum.
... Brazil, these products are classified as risk grade 2, with potential danger to health [15][16] [17]. ...
A simple, fast, low-cost, portable, and eco-friendly method using a spot test on a paper platform, together with diffuse reflectance spectroscopy, was developed and validated for the quantification of aluminum hydrochloride, a potential neurotoxic agent, in antiperspirant samples. The determination of aluminum hydrochloride was performed at a wavelength of 615 nm, by measuring consumption of the purple colorimetric reagent Alizarin S, due to reaction with aluminum. The linear range was from 10.0 to 125.0 mg L-1 and could be described by the equation: AR = 0.4479 - 0.002543 CAl (R = 0.999). The limits of detection (LOD) and quantification (LOQ) were 3.06 and 10.2 mg L-1, respectively. The method was specific, accurate, and repeatable, with relative standard deviation (RSD) <5.0%. The recovery was between 92.2 and 103.4%. The method was successfully used for the determination of aluminum hydrochloride in commercial antiperspirant samples, revealing concentrations below the maximum permitted by current legislation.
... However, association between Al exposure and Alzheimer's disease or autism is still questionable [8]. Moreover, the existing studies demonstrate a link between aluminium and breast cancer [9]. Evidence on the association between occupational aluminium exposure and pulmonary fibrosis [10], lung cancer [11], and neurological dysfunction [12] exist. ...
The objective of the present study was to assess the level of aluminium and toxic metals in hair of workers occupationally exposed to aluminium. 124 employees of the aluminium plant working in the hydrometallurgical (n = 43) and sintering units (n = 41), as well as 40 occupationally nonexposed controls were examined. Hair aluminium (Al), arsenic (As), beryllium (Be), cadmium (Cd), mercury (Hg), nickel (Ni), lead (Pb), and tin (Sn) content was assessed using inductively-coupled plasma mass spectrometry. The obtained data demonstrate that aluminium plant workers had significantly higher levels of hair Al (28.8 (15.4-58.6) vs 7.8 (4.3-14.2) μg/g, p < 0.001), Cd (0.053 (0.032 - 0.095) vs 0.025 (0.014 - 0.043) μg/g, p < 0.001) and Pb (0.672 (0.299-1.310) vs 0.322 (0.170 - 0.609) μg/g, p = 0.012) than the controls, respectively. Further analysis demonstrated that persons involved in different technological processes were characterized by distinct hair metal profiles. Hair Al, Be, Cd, Ni, Pb, and Sn levels in men working in the sintering unit of the aluminium plant exceeded the respective control values. In turn, workers of the hydrometallurgical unit were characterized by more than 2-fold higher levels of Al and Cd in hair as compared to the controls. The results of the present study demonstrate that workers of the aluminium plant are characterized by increased risk of Al as well as As, Cd, Pb, and Sn exposure.
... These exposures have been implicated in the emergence of several biochemical and metabolic pathologies. Several studies have described prooxidant effects (Ruipérez et al. 2012), modifications of the essential metal homeostasis (Walton 2012), double strand DNA breaks (Sappino et al. 2012), and altered release of some cytokines involved in major inflammatory pathways (Darbre et al. 2013;Mannello et al. 2013). Oxidative damage to cells in the murine hippocampus induced by Al has been clearly demonstrated (Ding and Yang 2010). ...
High Selenium Yeast (SeY) serves many important roles with respect to the maintenance of normal nervous system functioning. Studies have reported the nerve inflammation induced by Aluminum (Al) was associated with the increase of mortality. However, in-depth studies are required to verify the hypothesized neuro-protective efficacy of SeY against Al-induced cerebral damage through modulation of the inflammatory response. Here, mice were treated with SeY (0.1 mg/kg) and/or Al (10 mg/kg) by oral gavage for 28 days. Inflammation was assessed by histopathological examination and expression of biomarkers for inflammation. Furthermore, the oxidation-reduction levels and the NO production were assessed using diagnostic kits and RT-PCR. The data indicated that SeY significantly protected cerebrum against Al-induced pathological changes, in addition to the disordered expression of biomarkers of inflammation, the imbalance of oxidation-reduction, and the increase of NO production. Therefore, the chemoprotective potential of SeY against Al-induced cerebral inflammation via restore the levels of oxidation-reduction and the generation of NO was demonstrated.
... Cosmetic treatment of perspiration and odor has relied mainly on the incorporation of aluminium salts [35,36] supported by the addition of many types of cosmetic ingredients such as alcohols and plant extracts. Raising concerns over the presence of aluminium found in dementia patients brains [37] [11], breast cancer [38], and effects on the environment [30,39], the industry is slowly moving away from the use of such salts to more skin and environmentally friendly actives. Furthermore, since deodorants and antiperspirants clearly influence the axillary microbiome [40] alternative formulation strategies are under investigation. ...
Of all the natural functions of the skin, perspiration and its odorous consequences is one of the most lucrative challenges of the cosmetic industry, especially due to its social impact . Body odor and perspiration is deemed offensive in most cultures and cosmetic products to control this phenomenon are in high demand. The reduction of sweat and its resulting odor is normally addressed by antiperspirant formulations containing aluminium salts and standard antimicrobial actives. However concerns over environmental safety, cancer, health and wellbeing are driving innovation in new directions. A wider understanding of the potential positive and negative effects of antiperspirants and deodorants on the skins natural microbiome is becoming more appreciated, alongside a marketing desire for more elaborate claims. This has led to new formulations and different approaches within the confines of legislative requirements for study designs. Here we discuss sweat odor and perspiration, and examine both standard and new developed approaches in clinical testing for claims substantiation within the context of product efficacy, their effect on the skin‘s microbiome and legislative product claims requirements.
... Recently, we reported the possible effects of triclosan, a widely used anti-microbial agent, in potentiating epithelial to mesenchymal transition that may further facilitate the metastasis process (Winitthana et al. 2014). Other reports have also revealed that many chemical compounds present in daily products might confer cancer cells toward more aggressive phenotypes (Khanna et al. 2014;Darbre et al. 2013). Therefore, it is reasonable that novel knowledge on compound toxicology should be frequently updated to prevent any adverse outcomes from exposure to the compounds, especially in cancer patients. ...
Exposure to compounds with cancer-potentiating effects can contribute to the progression of cancer. Herein we have discovered for the first time that benzophenone-3 (BP-3), a chemical used as sunscreen in various cosmetic products, enhances the ability of lung cancer cells to undergo metastasis. The exposure of the lung cancer cells to BP-3 at non-toxic concentrations significantly increased the number of anoikis resistant cells in a dose-dependent manner. Also, BP-3 increased the growth rate as well as the number of colonies accessed by anchorage-independent growth assay. We found that the underlying mechanisms of such behaviors were the epithelial to mesenchymal transition (EMT) process of cancer cells, and the increase in caveolin-1 (Cav-1) expression. As both mechanistic events mediated anoikis resistance via augmentation of cellular survival signals, our results further revealed that the BP-3 treatment significantly up-regulated extracellular-signal-regulated kinase (ERK). Also, such compounds increased the cellular levels of anti-apoptotic Bcl-2 and Mcl-1 proteins. As the presence of a substantial level of BP-3 in plasma of the consumers has been reported, this finding may facilitate further investigations that lead to better understanding and evidence concerning the safety of use in cancer patients.
... Being a non-essential element, Al was shown to be toxic for humans (Exley, 2013), resulting in adverse health effects (Crisponi et al., 2011) including bone pathology (Klein, 2019) and breast cancer (Darbre et al., 2013). Our data also demonstrated the association between obesity (Tinkov et al., 2019), laboratory markers of metabolic syndrome and Al exposure markers . ...
Recent studies have demonstrated that brain may be considered as the target for aluminium (Al) toxicity, resulting in development of neurodegenerative and neurodevelopmental disorders. However, the particular mechanisms of Al neurotoxicity and their role in Al-associated neurological disorders are still debatable. The neurotoxic effect of Al exposure is mediated by its common toxic properties including prooxidant, proinflammatory, proapoptotic activity that are reported for a variety of cell lines and tissues, as well as more specific “neurotropic” effects namely interference with neurotransmitter metabolism and neuronal cytoskeleton. Although specific treatment of Al toxicity is not developed, Al chelation as well as compounds targeting molecular mechanisms of Al neurotoxicity (trace elements, polyphenols, phytoextracts, etc.) may be considered as therapeutic strategies to counteract Al neurotoxicity. However, further studies are required to unravel the particular role of Al in neurological diseases and specific treatment agents.
... 16−18 Furthermore, free iron resulting from an ineffective iron metabolism and the formation of an aluminum superoxide radical complex as a promotor have been described to react following the Fenton reaction, creating hydroxyl radicals. 16,19 These radicals have a pro-oxidative effect and can induce lipid peroxidation and DNA and biomolecule damages. With the ongoing discussion concerning the potential health risks associated with aluminum, world health authorities, e.g., the European Food Safety Authority (EFSA), have set thresholds for intake levels that should avoid the negative effects associated with Al. ...
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.
... Aluminium has neurotoxic effects and has long been suspected as one of the factors causing the Alzheimer's and Parkinson's disease [12]. Al 3+ can cause osteomalacia [13] and also acts as a metalloestrogen facilitating the gene-expression in breast cancer cell and therefore its growth [14][15][16][17]. The World Health Organization (WHO) prescribed the average human intake of aluminium as around 3-10 mg/day and its limit in drinking water should be less than 7.41 μM [18][19][20][21]. ...
A potent fluorescence ‘turn-on’ receptor (HL) based on rhodamine and coumarin moieties for the detection of Hg²⁺ and Al³⁺ is synthesized by condensation of rhodamine 6G hydrazide and 4-hydroxy-3-acetylcoumarin. In presence of Al³⁺ and/or Hg²⁺ the receptor (HL) exhibits deep pink colouration and a sharp band at 528 nm is appeared in UV–vis titration. Upon gradual addition of Al³⁺ and/or Hg²⁺ to the solution of HL significant enhancement of fluorescence intensity is observed at 564 nm in MeCN:H2O (1:5, v/v) medium. The receptor is strongly bound to Al³⁺ and/or Hg²⁺ and the association constants (Ka) are found to be 1.74 × 10⁴ and 1.04 × 10⁴ M− 1 for Al³⁺ and Hg²⁺ respectively.
Graphical Abstract
A potent fluorescence ‘turn-on’ receptor (HL) based on rhodamine and coumarin moieties for the detection of Hg²⁺ and Al³⁺ is synthesized and characterized. In presence of Al³⁺ and/or Hg²⁺ the receptor (HL) exhibits deep pink colouration and significant enhancement of fluorescence intensity is observed at 564 nm in MeCN:H2O (1:5, v/v) medium. The receptor is strongly bound to Al³⁺ and/or Hg²⁺ and the association constants (Ka) are found to be 1.74 × 10⁴ and 1.04 × 10⁴ M− 1 for Al³⁺ and Hg²⁺ respectively.
... Accumulating evidence from in vitro and in vivo experimental studies, as well as epidemiological observations, demonstrate that increased exposures to Al can lead to a number of adverse health effects [3]. Al has been postulated to induce oxidative stress in various cell types [4,5], interfere with estrogen receptors [6], support osteomalacia via phosphate deficiency, impair calcium uptake and engender dysfunctional osteoblast proliferation [7], as well as to alter iron homeostasis by disrupting intestinal Fe absorption and normal tissue ferritin levels [8]. Of highest concern is that studies on Al uptake have revealed a neurotoxic action that is potentially implicated in different neurodegenerative disorders, including encephalopathy, Alzheimer's disease and multiple sclerosis [9][10][11]. ...
Introduction: Alcohol overuse may be related to increased aluminum (Al) exposure, the brain accumulation of which contributes to dementia. However, some reports indicate that silicon (Si) may have a protective role over Al-induced toxicity. Still, no study has ever explored the brain content of Al and Si in alcoholic use disorder (AUD). Materials and methods: To fill this gap, the present study employed inductively coupled plasma optical emission spectrometry to investigate levels of Al and Si in 10 brain regions and in the liver of AUD patients (n = 31) and control (n = 32) post-mortem. Results: Al content was detected only in AUD patients at mean ± SD total brain content of 1.59 ± 1.19 mg/kg, with the highest levels in the thalamus (4.05 ± 12.7 mg/kg, FTH), inferior longitudinal fasciculus (3.48 ± 9.67 mg/kg, ILF), insula (2.41 ± 4.10 mg/kg) and superior longitudinal fasciculus (1.08 ± 2.30 mg/kg). Si content displayed no difference between AUD and control, except for FTH. Positive inter-region correlations between the content of both elements were identified in the cingulate cortex, hippocampus, and ILF. Conclusions: The findings of this study suggest that AUD patients may potentially be prone to Al-induced neurodegeneration in their brain-although this hypothesis requires further exploration.
... Aluminum ion (Al 3+ ) can accumulate in the human body through food chains, and it will be enriched in the organism eventually. Accumulation of excessive amount of Al 3+ in human body can lead to a variety of diseases, such as Alzheimer's disease and Parkinson's disease [8][9][10][11][12][13][14][15][16]. Since there is a close association between Al 3+ and people's health, it is crucial to develop several highly selective and convenient tools for the detection of Al 3+ . ...
... Cosmetic treatment of perspiration and odor has relied mainly on the incorporation of aluminum salts (7) supported by the addition of many types of cosmetic antimicrobial ingredients such as alcohols and specific plant extracts. Given concerns over the presence of aluminum found in dementia patients brains (8), breast cancer (9), and effects on the environment (6, 10), the industry is rapidly moving away from the use of such salts to focus more on well-being and environmentally friendly actives. Furthermore, since deodorants and antiperspirants clearly influence the axillary microbiome (11) A lthough a natural function of the skin, perspiration and the odor it produces is considered offensive in many cultures, and consequently products addressing this problem are in high demand. ...
Although a natural function of the skin, perspiration and the odor it produces is considered offensive in many cultures, and consequently products addressing this problem are in high demand. Antiperspirants and most deodorants are normally formulated with aluminum salts. However concerns over environmental safety, health and wellbeing are driving innovation in new directions. A wider appreciation of the effects of antiperspirants and deodorants on the skins natural microbiome is taking centre stage, and the desire for more natural microbiome friendly products is leading to new development, both in formulations and performance testing methods. In order to investigate the efficacy of antiperspirants at the early stages of development, a screening test based on the gravimetric sweat determination, by applying cotton pads to harvest the sweat, is preferably used. However, this standard test does not work with all aluminum-free antiperspirants, especially those containing film forming actives where the contact with cotton pads may lead to a measurement bias. In the present work
we describe a new screening method using Capacitive Contact Imaging in which the sweat reducing effect of a new generation of non-plug forming actives can be evaluated without application of pads to sample the sweat. In evaluating the method, a differentiation between the effect of different substances was observed. In summary, Capacitive Contact Imaging with appropriate image analysis is a reproducible and innovative approach for the efficacy of non-aluminum containing, as well as aluminum containing antiperspirants, especially for those for which gravimetric methods fail to
produce accurate results.
... It crosses Blood Brain Barrier (BBB) and persists in the brain for up to five months (Tomljenovic, 2011;Ekong et al., 2017). Rats exposed to low levels of AlCl 3 in the drinking water showed higher aluminum level in the brain than the control group (Darbre et al., 2013). Moreover, it induces BBB permeability leading to aluminum and other substances enter the brain (Cabus et al., 2015). ...
Background
Alzheimer’s disease (AD) is the most common cause of dementia in elderly. Quercetin is a well-known flavonoid with low bioavailability. Recently, quercetin nanoparticles (QNPs) has been shown to have a better bioavailability.
Aims
This study aimed to investigate the protective and therapeutic effects of QNPs in Aluminum chloride (AlCl3) induced animal model of AD.
Materials and Methods
AD was induced in rats by oral administration of AlCl3 (100 mg/kg/day) for 42 days. QNPs (30 mg/kg) was given along with AlCl3 in the prophylactic group and following AD induction in the treated group. Hippocampi were harvested for assessments of the structural and ultrastructural changes using histological and histochemical approaches.
Results and Discussion
AD hippocampi showed a prominent structural and ultrastructural disorders both neuronal and extraneuronal. Including neuronal degeneration, formation of APs and NFTs, downregulation of tyrosine hydroxylase (TH), astrogliosis and inhibition of the proliferative activity (all P ≤ 0.05). Electron microscopy showed signs of neuronal degeneration with microglia and astrocyte activation and disruption of myelination and Blood Brain Barrier (BBB). Interestingly, QNPs administration remarkably reduced the neuronal degenerative changes, APs and NFTs formation (all P ≤ 0.05). Furthermore, it showed signs of regeneration (all P ≤ 0.05) and upregulation of TH. The effect was profound in the prophylactic group. Thus, QNPs reduced the damaging effect of AlCl3 on hippocampal neurons at the molecular, cellular and subcellular levels.
Conclusion
For the best of our knowledge this is the first study to show a prophylactic and therapeutic effect for QNPs in AD model. This might open the gate for further research and provide a new line for therapeutic intervention in AD.
... Therefore can be measured in the urine and to feces. There are insufficient data to relate aluminum exposure levels with blood or ruin levels (31). Based on what has been discussed above, we have analyzed the aluminum element in both the blood and urine and found in the following table (2). ...
To investigate the concentration and role of certain important elements in 55 patients women diagnosis with breast cancer. The patient groups which divided into 2 groups: (30 patients with premenopausal) and (25 patients with postmenopausal) aged (20-60) years have been examined and formed the initial study group trace metals are essential to normal human homeostasis. When present in an abnormal expression, they contribute in many pathological processes. Our aim was to investigate the serum and urine concentration of some important elements Copper (Cu). Zinc (Zn). Selenium (Se). Aluminum (Al). Chromium (Cr). Lead (Ld). and Magnesium (Mg) of the patients with breast cancer, and (50) healthy control women it is found that there were statistically increased significant of (Copper, Lead. and Aluminum) in postmenopausal patients as compared with controls and pre-menopausal patients with p≤0.001. While the serum levels of (Zinc. Selenium. Chromium and Magnesium) in pre-menopause patients was increased significantly different from control and postmenopausal patients. There was no significant difference in the serum level of (Zinc. Selenium. Lead and Magnesium) between the groups of breast cancer patients. The urinary minerals that exhibited the levels of (Cu (in pre). Zinc (in post), Selenium (in pre), Lead (in pre and post). Chromium (in post) and Aluminum (in pre-post), a significant difference (increased) from controls
... In a case control study , the use of underarm cosmetic products containing Al was significantly associated with breast cancer incidence and the Al levels in breast tissues were significantly higher in breast cancer cases than controls (5.8 versus 3.8 nmol/g). 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). ...
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.
... Micronuclei frequency and apoptotic and necrotic percentages were significantly increased in zinc deficient and zinc-oversupplied cultures [81]. Excesses in aluminum or copper can also prompt the accumulation of DNA damage [82,83]. However, another study by Fenech et al. [84] found that supplementing with vitamin E, calcium, folate, retinol, and nicotinic acid was associated in each case with a significant decrease in genomic damage, as indicated by reduced micronuclei frequency; this study also correlated an increase in micronuclei formation with high intakes of certain micronutrients, including riboflavin, pantothenic acid, and biotin. ...
Pediatric leukemias are the most prevalent cancers affecting children in developed societies, with childhood acute lymphoblastic leukemia (ALL) being the most common subtype. As diet is a likely modulator of many diseases, this review focuses on the potential for diet to influence the incidence and progression of childhood ALL. In particular, the potential effect of diets on genome stability and immunity during the prenatal and postnatal stages of early childhood development are discussed. Maternal diet plays an integral role in shaping the bodily composition of the newborn, and thus may influence fetal genome stability and immune system development. Indeed, higher birth weights of newborns are associated with increased risk of ALL, which suggests in-utero biology may shape the evolution of preleukemic clones. Postnatally, the ingestion of maternal breastmilk both nourishes the infant, and provides essential components that strengthen and educate the developing immune system. Consistently, breast-feeding associates with decreased risk of ALL development. For children already suffering from ALL, certain dietary regimens have been proposed. These regimens, which have been validated in both animals and humans, alter the internal hormonal environment. Thus, hormonal regulation by diet may shape childhood metabolism and immunity in a manner that is detrimental to the evolution or expansion of preleukemic and leukemic ALL clones.
... In turn, its ion (Al 3+ ) which is released under low pH reveals toxicity in biological systems. As demonstrated in vitro and in vivo, and supported by epidemiological studies, increased exposures to Al can be associated with various adverse health effects (Exley 2016) encompassing the induction of oxidative stress (Yuan et al. 2012;Cheraghi et al. 2017), agonistic action on estrogen receptors (Darbre et al. 2013), impairment of the calcium and phosphate burden (Gura 2010), alteration of iron homeostasis through disruption of its intestinal absorption and normal tissue ferritin levels (Rosenlöf et al. 1990), and neurotoxicity. As shown, subjects with encephalopathy, Alzheimer's disease, multiple sclerosis, and alcoholic use disorder reveal increased brain Al levels (Rondeau et al. 2000;Nakamura et al. 2000;Mold et al. 2018a;Mold et al. 2018b;Grochowski et al. 2019). ...
There is limited information on whether metals such as aluminum (Al) can migrate from orthodontic braces to saliva and subsequently contribute to its exposure in humans. This study aimed to assess this experimentally by incubating elastomeric orthodontic ligatures in artificial saliva for 30 days and other components of orthodontic braces (brackets, arch wires, and retainers) up to 180 days. As demonstrated, significantly higher levels of Al were leached from elastomeric ligatures (mean ± SD 28.2 ± 6.8 μg compared with their stainless steel counterparts (3.6 ± 0.1 μg) during 30 days. The higher the incubation time, the greater levels of Al leaching to artificial saliva were observed with the highest levels found for CNA β arch wire (252 ± 12 μg), Ni-Ti-Al arch wire (224 ± 11 μg), ceramic brackets (199 ± 10 μg), stainless steel arch wire (108 ± 5 μg), and metallic brackets (81.0 ± 4.2 μg) after 180 days of incubation. However, considering the tolerable weekly intake (TWI) established by the European Food Safety Authority, the intraoral use of orthodontic braces considered in this study would in the worst case constitute 0.04% and 0.09% of TWI in 70-kg adults and 30-kg children, respectively. In conclusion, the orthodontic braces considered in this study have no contribution to Al exposure in humans and can be considered safe in this regard.
... In a case control study , the use of underarm cosmetic products containing Al was significantly associated with breast cancer incidence and the Al levels in breast tissues were significantly higher in breast cancer cases than controls (5.8 versus 3.8 nmol/g). 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). ...
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.
A novel water-soluble chromone Schiff base derivatives bearing polyhydroxylated moiety were prepared and applied for specific recognition of metal ions in aqueous medium. Their selective fluorescence response to Al(III) over a variety of other biologically important metal ions were demonstrated. Electronic parameters of the sensors were also studied by quantum chemical computations.
A highly sensitive and selective coumarin based chemosensor H2L for the efficient detection of Al3+ has been developed. The synthesized chemosensor H2L is efficient in detecting Al3+ over other metal ions which are commonly obtained in various physiological and environmental samples. H2L shows fluorescence ‘turn-on’ response at 610 nm in presence of Al3+ , without the interference of other metal ions. The resulting H2L-Al3+ complex behave as a sequential chemosensor for F-, by showing quenching of emission intensity upon addition of F- to it. This quenching of emission intensity is only specific for F- and is not hampered due to the presence of other anions that commonly coexist with F- in various environmental solutions. Theoretical calculations using DFT/B3LYP method has been used to get insight into the sensing mechanism as well as electronic structure of the synthesized chemosensor H2L. H2L is efficient in detecting Al3+ in the intracellular region of human A549 cell and also exhibits an INHIBIT logic gate with Al3+ and F- as chemical inputs by monitoring the emission mode at 610 nm.
The human population is exposed to aluminium (Al) from diet, antacids and vaccine adjuvants, but frequent application of Al-based salts to the underarm as antiperspirant adds a high additional exposure directly to the local area of the human breast. Coincidentally the upper outer quadrant of the breast is where there is also a disproportionately high incidence of breast cysts and breast cancer. Al has been measured in human breast tissues/fluids at higher levels than in blood, and experimental evidence suggests that at physiologically relevant concentrations, Al can adversely impact on human breast epithelial cell biology. Gross cystic breast disease is the most common benign disorder of the breast and evidence is presented that Al may be a causative factor in formation of breast cysts. Evidence is also reviewed that Al can enable the development of multiple hallmarks associated with cancer in breast cells, in particular that it can cause genomic instability and inappropriate proliferation in human breast epithelial cells, and can increase migration and invasion of human breast cancer cells. In addition, Al is a metalloestrogen and oestrogen is a risk factor for breast cancer known to influence multiple hallmarks. The microenvironment is established as another determinant of breast cancer development and Al has been shown to cause adverse alterations to the breast microenvironment. If current usage patterns of Al-based antiperspirant salts contribute to causation of breast cysts and breast cancer, then reduction in exposure would offer a strategy for prevention, and regulatory review is now justified.
We are living in the 'aluminium age'. Human exposure to aluminium is inevitable and, perhaps, inestimable. Aluminium's free metal cation, Alaq(3+), is highly biologically reactive and biologically available aluminium is non-essential and essentially toxic. Biologically reactive aluminium is present throughout the human body and while, rarely, it can be acutely toxic, much less is understood about chronic aluminium intoxication. Herein the question is asked as to how to diagnose aluminium toxicity in an individual. While there are as yet, no unequivocal answers to this problem, there are procedures to follow to ascertain the nature of human exposure to aluminium. It is also important to recognise critical factors in exposure regimes and specifically that not all forms of aluminium are toxicologically equivalent and not all routes of exposure are equivalent in their delivery of aluminium to target sites. To ascertain if Alzheimer's disease is a symptom of chronic aluminium intoxication over decades or breast cancer is aggravated by the topical application of an aluminium salt or if autism could result from an immune cascade initiated by an aluminium adjuvant requires that each of these is considered independently and in the light of the most up to date scientific evidence. The aluminium age has taught us that there are no inevitabilities where chronic aluminium toxicity is concerned though there are clear possibilities and these require proving or discounting but not simply ignored.
Certain environmental chemicals may accumulate in human serum and tissues eliciting estrogenic and/or carcinogenic effects. Therefore, there is heightened interest in determining whether environmental chemicals may increase the risk for endocrine-related tumors like breast cancer. For instance, metals as cadmium, zinc, copper, iron, nickel and aluminum have been shown to mimic estrogen action. Moreover, the exposure to these chemicals has been reported to stimulate diverse malignancies including breast cancer, which is the most common tumor in women worldwide. In this review, we summarize the epidemiologic and experimental evidence regarding the association between the exposure to some trace elements and breast cancer risk. We also address recent insights on the molecular mechanisms involved by metals in breast tumorigenesis.
In this study, a novel chromone-derived Schiff-base ligand which was called bis(6-hydroxychromone-3-methylidene)-o-phenylenediimine (1) was designed, synthesized, and evaluated as an Al³⁺ “turn on” fluorescent probe. This probe 1 showed good selectivity and high sensitivity towards Al³⁺ in the presence of most metal ions, and a remarkable enhancement by about 30.91-fold in fluorescence emission intensity at 459 nm was observed with addition of 1 equiv of Al³⁺, which was attributed to the inhibition of photoinduced electron-transfer (PET) phenomenon and C[dbnd]N isomerization process at the excited state. Moreover, the fluorescence response of 1 to Al³⁺ was nearly completed within 10 min. Thus, this probe 1 could be utilized for sensing and monitoring Al³⁺ in environmental and biological systems for real-time detection.
Dermal absorption of components of personal care products (PCPs) may contribute to breast cancer development. Cyclic volatile methylsiloxanes (cVMS) are used widely in the formulation of PCPs, and their presence has been recently detected in human blood. The objectives of this study were to investigate any genotoxic effects after short- (1 week) or longer-term (30 weeks) exposure to hexamethylcyclotrisiloxane (D3), octamethylcyclotetrasiloxane (D4) or decamethylcyclopentasiloxane (D5) in MCF-10 A and MCF-10F immortalized non-transformed human breast epithelial cells. Genotoxic effects were assessed by an ability of cells to grow in suspension culture, from DNA damage measured by comet assays, and from a reduction in levels of DNA repair proteins measured by RT-PCR and western immunoblotting. Dose-dependent anchorage-independent growth in methocel culture was observed after exposure to D3 (10(-) (13) M-10(-5) M) and D4/D5 (10(-) (9) M-10(-5) M). DNA damage was measured by the comet assay after 1-h exposure to D3 (10(-) (6) M-10(-5) M) and D4 (10(-5) M). BRCA1 mRNA and BRCA1 protein levels were reduced after 30-week exposure to 10(-5) M D4 and D5 in both cell lines. Reduced levels of mRNAs for other DNA repair proteins (BRCA2, ATM, ATR, CHK1 and CHK2) were also observed after exposure to 10(-5) M D5 in both cell lines, and some reductions after exposure to D3 and D4. If cVMS can not only enable anchorage-independent growth of non-transformed breast epithelial cells and damage DNA, but also compromise DNA repair systems, then there is the potential for them to impact on breast carcinogenesis. Further risk assessment now requires information concerning the extent to which cVMS may be present in human breast tissues. Copyright © 2016 John Wiley & Sons, Ltd.
Microalgae biomass as a promising bioenergy feedstock is considered to have huge potential to produce biofuels. However, a main barrier in microalgae biomass production is the economical and efficient harvesting and dewatering process of microalgae in large scale, which significantly restricts the development of microalgae biotechnology industries. Ballasted flotation, can be viewed as inverted ballasted sedimentation techniques, has recently been used to harvest microalgae. In this process, a low-density material (LDM) is used to replace the bubbles in the dissolved air flotation process and attach to the microalgae cells, so that the microalgae cells float to the liquid surface and implement solid-liquid separation. This paper reviews the research progress of ballasted flotation technique for microalgae harvesting by revealing the principles of ballasted flotation process, summarizing the advantages and disadvantages, analyzing the operating parameters and energy consumption. This review expands our understanding about ballasted flotation, intends to provide guidance for the future research and practical applications of ballasted flotation. Finally, this review also suggests the directions for challenges and further perspectives of ballasted flotation for microalgae harvesting in the development of new LDMs and flocculants, the detachment of microalgae cell-LDM aggregates, the recovery and utilization of the harvest water, etc.
Over the last years, focused interest in aluminum has been heightened by recent studies regarding its health effects. The possible relation with chronic diseases makes it convenient to address more in depth the reactivity of aluminum with biologically relevant molecules. The present work investigates the interaction of aluminum ion with two synthetic RNAs, poly(rA) and poly(rU), through a detailed thermodynamic and kinetic study. Trivalent aluminum ion was kept in solution by complexation with cacodylate anion, even at neutral pH, thus rendering feasible the study with biological molecules. The results obtained with spectrophotometry, circular dichroism, viscometry and thermal stability measurements indicate that aluminium strongly interacts with single and duplex RNA structures. The kinetic experiments point up that, even though cacodylate was required to keep the metal in solution, actually it inhibits the reaction of aluminum with RNA as it converts the metal into an unreactive dimer species. Notably, further interaction occurred under excess of aluminum/cacodylate complex, inducing aggregation of single-stranded RNAs. An analysis of the kinetic data has shown that the modes of aggregation of the two RNAs differ and such a difference can be ascribed to the diverse polynucleotide secondary structures. The observed stabilization of multiple-stranded systems by aluminum can be of interest for the use of this metal in the study of non-canonical nucleic acid structures.
Aluminum salts are widely used as the active antiperspirant in underarm cosmetic. Experimental observations indicate that its long term application may correlate with breast cancer development and progression. This action is proposed to be attributed, among others, to aluminum possible estrogen-like activities. In this study we showed that aluminum, in the form of aluminum chlorohydrate (ACH), caused increase in estrogen receptor alpha (ERα) protein levels, in ERα-positive MCF-7 cells. This effect was accompanied by moderate activation of Estrogen Response Elements (ERE)-driven reporter gene expression and 20%-50% increase in certain estrogen responsive, ERE-independent genes expression. Genes affected were ERα, p53, cyclin D1, and c-fos, crucial regulators of breast cancer development and progression. ACH-induced genes expression was eliminated in the presence of the estrogen antagonist: ICI 182780, in MCF-7 cells, whereas it was not observed in ERα-negative MDA-MB-231 breast cancer cells, indicating aluminum interference with estrogen signaling. Moreover, ACH caused increase in the perinuclear localization of estrogen receptor alpha in MCF-7 breast cancer cells and increase in the mitochondrial Bcl-2 protein, possibly affecting receptors-mediated mitochondrial actions and mitochondrial-dependent apoptosis. ACH-induced perinuclear localization of estrogen receptor beta was also observed in MDA-MB-231. Our findings indicate that aluminum actions on estrogen receptors protein level and subcellular localization possibly affect receptors-mediated actions and thus, aluminum interference with estrogen signaling.
Background:
Aluminum exposure may originate from numerous sources, including antiperspirants. Aluminum toxicity can cause a wide range of neurological impairments. Infants are exposed to aluminum through human milk (HM), formulas, total-parenteral-nutrition and vaccines. Due to potential risk of toxicity to both infants and women, it has been advised that lactating women decrease their use of aluminum-based products and antiperspirants. Our study aimed to determine whether the use of aluminum-based antiperspirants (ABA) affects aluminum levels in HM.
Methods:
This cross-sectional study included healthy mothers who exclusively breastfed infants (1 week to 5 months). Questionnaires were used to collect data on demographics, antiperspirant use and aluminum exposure. Mothers were instructed to express HM during the morning at first breastfeeding session. Aluminum levels were measured by atomic absorption spectrometry with a 5 ppb limit of detection.
Results:
Fifteen of the 58 (26%) recruited mothers used an aluminum-free antiperspirant (AFA) and 43 (74%) used an ABA. The range of aluminum concentration in HM was 0-100.8 μg/L (mean 11.4 ± 17.4 μg/L). The median aluminum level (Q1-Q3) was 6.5 μg/L (5.2-11.9) and 5.2 μg/L (3.46-9.4) in the AFA and ABA groups, respectively (p = 0.19). The aluminum levels were not affected by maternal age, education, diet, number of children, infant age, lactation stage or self-reported aluminum exposure.
Conclusion:
The data from this preliminary study demonstrate that the use of an ABA by lactating mothers does not increase their HM aluminum content. Additional studies with a larger cohort are warranted to confirm these findings.
Hyperhidrosis (HH) is a chronic disorder of excess sweat production that may have a significant adverse effect on quality of life. A variety of treatment modalities currently exist to manage HH. Initial treatment includes lifestyle and behavioral recommendations. Antiperspirants are regarded as the first-line therapy for primary focal HH and can provide significant benefit. Iontophoresis is the primary remedy for palmar and plantar HH. Botulinum toxin injections are administered at the dermal-subcutaneous junction and serve as a safe and effective treatment option for focal HH. Oral systemic agents are reserved for treatment-resistant cases or for generalized HH. Energy-delivering devices such as lasers, ultrasound technology, microwave thermolysis, and fractional microneedle radiofrequency may also be utilized to reduce focal sweating. Surgery may be considered when more conservative treatments have failed. Local surgical techniques, particularly for axillary HH, include excision, curettage, liposuction, or a combination of these techniques. Sympathectomy is the treatment of last resort when conservative treatments are unsuccessful or intolerable, and after accepting secondary compensatory HH as a potential complication. A review of treatment modalities for HH and a sequenced approach are presented.
Human serum transferrin (hTF) is an iron binding protein with the primary task of ensuring well-controlled transport of Fe ³⁺ -ions in the bloodstream. Furthermore, hTF has been identified as a key...
Upon excitation of the visible light, probes show colorimetric and fluorescent responses to the specific metal ion, which can be easily detected by the naked eye. Owing to the excitation of the visible light at 423 nm, a novel and simple Schiff-base receptor based chromone derivative called 7-methoxychromone-3-carbaldehyde-(indole-3-formyl) hydrazone (MCIH2) had been investigated as a selective and sensitive probe for Al ³⁺ with colorimetric and fluorescent responses. Upon addition of Al ³⁺ to compound MCIH2 solution, compound MCIH2 could respond to Al ³⁺ with a good selective colorimetric signal, which was easily observed from colorless to yellow-green by the naked eye. Furthermore, a remarkable fluorescence emission enhancement with an “OFF-ON” signal by over 700-fold was triggered, but other various metal ions had no such significant effects on the fluorescence emission. In addition, the detection limit of compound MCIH2 for recognizing Al ³⁺ was evaluated to be as low as 1 × 10 ⁻⁷ M level, which was sufficiently low for sensing Al ³⁺ widely distributed in various environmental and biological systems.
(E)-N′-((2-Hydroxynaphthalen-1-yl)methylene)picolinohydrazide (H-PNAP) shows aggregation-induced emission (AIE) strictly in a 90% water/MeOH (v/v) mixture at 540 nm, and the solid-state emission is blue-shifted to 509 nm upon excitation at 400 nm. The AIE activity of H-PNAP is selectively quenched by 2,4,6-trinitrophenol (TNP) and 2,4-dinitrophenol (DNP) out of different nitroaromatic compounds with a limit of detection (LOD) of 7.79 × 10 ⁻⁷ and 9.08 × 10 ⁻⁷ M, respectively. The probe is nonemissive in aqueous medium (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, HEPES buffer, pH 7.2); however, it shows a strong emission to Al ³⁺ (λ em , 490 nm) in the presence of 17 other biological metal ions, and the LOD is 2.09 nM which is far below the WHO recommended value (7.41 mM). The emission of the [Al(PNAP)(NO 3 ) 2 ] complex is quenched by HF 2⁻ (F ⁻ and PO 4³⁻ are weak quencher), and the LOD is as low as 15 nM. The probable mechanism of the sensing feature of the probe has been authenticated by ¹ H nuclear magnetic resonance titration, mass spectrometry, Fourier transform infrared spectroscopy, Benesi-Hildebrand plot, and Job's plot in each case. The probe has some practical applications such as recovery of Al ³⁺ from the drinking water sample, construction of the INHIBIT logic gate, and detection kits for Al ³⁺ and TNP/DNP by simple paper test strips. The probe, H-PNAP, has successfully been applied to the detection of intracellular Al ³⁺ and HF 2⁻ ions in the human breast cancer cell, MDA-MB-468.
Quinolinyl-azo-naphthol (HL) is a selective turn-on chemosensor to Al3+ in presence of other ions and the excitation at visible light (537 nm) shows 750 fold enhancement of emission at 612 nm. The limit of detection (LOD) is 0.69 nM (3 method), which is far below the WHO recommended value of Al3+ in drinking water (7.41 µM). The composition of the isolated complex [AlL2]+ is supported by ESI-MS spectral data and Job’s plot. Upon addition of aqueous F- to [AlL2]+ solution the emission intensity is quenched and LOD of F- is 0.63 nM. HL is thus instrumental for the designing of potable kits for the detection of fluoride contamination in drinking water. The probe undergoes azo-hydrazo tautomerization and also exhibits an INHIBIT logic gate with Al3+ and F− as chemical inputs by monitoring the emission mode at 612 nm.
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
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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.
Aluminum and mercury are environmentally ubiquitous. Individually they are both neurotoxic elements with shared neuro-pathogenic pathways: oxidative stress, altered neurotransmission, and disruption of the neuroendocrine and immune systems. In the infant, Al and Hg differ in type of exposure, absorption, distribution (brain access), and metabolism. In environmentally associated exposure (breast milk and infant formulas) their co-occurrences fluctuate randomly, but in Thimerosal-containing vaccines (TCVs) they occur combined in a proprietary ratio; in these cases, low-doses of Thimerosal-ethylmercury (EtHg) and adjuvant-Al present the most widespread binary mixture in less developed countries. Although experimental studies at low doses of the binary Hg and Al mixture are rare, when studied individually they have been shown to affect neurological outcomes negatively. In in vitro systems, comparative neurotoxicity between Al and Hg varies in relation to the measured parameters but seems less for Al than for Hg. While neurotoxicity of environmental Hg (mainly fish methyl-Hg, MeHg) is associated with neurobehavioral outcomes in children, environmental Al is not associated, except in certain clinical conditions. Therefore, the issues of their neurotoxic effects (singly or combined) are discussed. In the infant (up to six months) the organic-Hg and Al body burdens from a full TCV schedule are estimated to reach levels higher than that originating from breastfeeding or from high aluminum soy-based formulas. Despite worldwide exposure to both Al and Hg (inorganic Hg, MeHg, and Thimerosal/EtHg), our knowledge on this combined exposure is insufficient to predict their combined neurotoxic effects (and with other co-occurring neurotoxicants).
A fluorescence sensor RBKB with high selectivity and sensitivity to Al³⁺ was designed and synthesized. UV-Vis and fluorescence spectra showed that the probe had a good response to Al³⁺ in EtOH/H2O (1:1, v/v) solution and the response time is very short. The process of detecting Al³⁺ is accompanied by the probe solution changing from colorless to pink, which has a good visual effect. The reversible type of the probe and Al³⁺ was confirmed by adding EDTA. Meanwhile, the probe has a low detection limit of 0.177 μM. In addition, the probe can be used for the detection of Al³⁺ in actual environmental water samples with a high recovery rate. It is worth mentioning that RBKB can be used to detect Al³⁺ in living cells, zebrafish, and plant tissues, which has high biological significance.
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 incidence of breast cancer has risen worldwide to unprecedented levels in recent decades, making it now the major cancer of women in many parts of the world.1 Although diet, alcohol, radiation and inherited loss of BRCA1/2 genes have all been associated with increased incidence, the main identified risk factors are life exposure to hormones including physiological variations associated with puberty/pregnancy/menopause,1 personal choice of use of hormonal contraceptives2 and/or hormone replacement therapy.3–6 On this basis, exposure of the human breast to the many environmental pollutant chemicals capable of mimicking or interfering with oestrogen action7 should also be of concern.8 Hundreds of such environmental chemicals have now been measured in human breast tissue from a range of dietary and domestic exposure sources7 ,9 including persistent organochlorine pollutants (POPs),10 polybrominated diphenylethers and polybromobiphenyls,11 polychlorinated biphenyls,12 dioxins,13 alkyl phenols,14 bisphenol-A and chlorinated derivatives,15 as well as other less lipophilic compounds such as parabens (alkyl esters of p -hydroxybenzoic acid),16 but studies investigating any association between raised levels of such compounds and the development of breast cancer remain inconclusive.7–16 However, the functionality of these chemicals has continued to be assessed on the basis of individual chemicals rather than the environmental reality of long-term low-dose exposure to complex mixtures. This misses the potential for individuals to have high concentrations of different compounds but with a common mechanism of action. It also misses the complex interactions between chemicals and physiological hormones which together may act to alter the internal homeostasis of the oestrogenic environment of mammary tissue.
Two recent papers17 ,18 have reported studies which shed light on this issue. The first paper17 presents evidence of exactly such a scenario in which 19 individual …
Many tumors, including breast cancer, are maintained by a subpopulation of cells that display stem cell properties, mediate metastasis, and contribute to treatment resistance. These cancer stem cells (CSCs) are regulated by complex interactions with the components of the tumor microenvironment - including mesenchymal stem cells, adipocytes, tumor associated fibroblasts, endothelial cells, and immune cells - through networks of cytokines and growth factors. Since these components have a direct influence on CSC properties, they represent attractive targets for therapeutic development.
Aluminum is an experimentally demonstrated neurotoxin and the most commonly used vaccine adjuvant. Despite almost 90 years of widespread use of aluminum adjuvants, medical science's understanding about their mechanisms of action is still remarkably poor. There is also a concerning scarcity of data on toxicology and pharmacokinetics of these compounds. In spite of this, the notion that aluminum in vaccines is safe appears to be widely accepted. Experimental research, however, clearly shows that aluminum adjuvants have a potential to induce serious immunological disorders in humans. In particular, aluminum in adjuvant form carries a risk for autoimmunity, long-term brain inflammation and associated neurological complications and may thus have profound and widespread adverse health consequences. In our opinion, the possibility that vaccine benefits may have been overrated and the risk of potential adverse effects underestimated, has not been rigorously evaluated in the medical and scientific community. We hope that the present paper will provide a framework for a much needed and long overdue assessment of this highly contentious medical issue.
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.
Protein carbonyl levels are the most frequently used biomarker of protein oxidation in several human diseases, including cancer. Breast cancer, a worldwide disease with increasing incidence, develops from ductal/lobular epithelium from which nipple aspirate fluid can be collected and analysed to assess tissue metabolic activity. Our aims were to perform an exploratory investigation on the protein carbonyl accumulation in breast secretions from healthy and cancer patients and its correlation with lipid peroxidation markers.
Protein carbonyls were determined by ELISA in 288 Nipple Aspirate Fluids (NAF) from Control, Pre-malignant and Cancer patients.
Significantly higher protein carbonyl concentration was found in NAF from breast cancer (BC) patients compared to Control subjects. Cancer patients accumulated in NAF significantly higher levels of carbonyls in post-menopausal condition. A significant inverse relationship between carbonyls and 8-F2alpha-isoprostanes in NAF was found in Cancer patients. NAF levels of protein carbonyls are significantly higher in women with pre-malignant conditions than in healthy subjects.
Our results support the hypothesis that oxidative stress in breast microenvironment plays a role in breast cancer; measurement of protein and lipid oxidative products in NAF may improve the identification of women at increased breast cancer risk.
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.
Clonal isolates of mouse 3T3 cells and primary rat embryo cells, recovered nonselectively after infection by simian virus 40 (SV40), have been tested for tumorigenicity in the immune-deficient nude mice in order to determine the cellular growth properties in vitro specifically correlated with neoplastic growth in vivo. In addition, mouse 3T3 cells transformed by murine sarcoma virus (MuSV, Kirsten strain), and revertants isolated from cells fully transformed by either SV40 or MuSV were also studied. Results suggest that the single cellular property consistently associated with tumorigenicity in nude mice is the acquisition by virus-transformed cells of the ability to proliferate in vitro in the absence of anchorage. Other cellular parameters of virus-induced transformation, such as lack of sensitivity to high cell density and the capacity to grow in low serum concentration, are dissociable from cellular tumorigeneicity. This conclusion is supported further by the demonstration that specific selection in vivo for tumorigenic cells from anchorage-dependent cells results in the isolation of anchorage-independent cells. Conversely, a single-step selection in vitro for anchorage-independent cells from nontumorigenic cells results in a simultaneous selection of highly tumorigenic subclones.
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.
Cellular effects of oestrogen are mediated by two intracellular receptors ERα and ERβ. However, to compare responses mediated through these two receptors, experimental models are needed where ERα and ERβ are individually stably overexpressed in the same cell type.
We compared the effects of stable overexpression of ERα and ERβ in the MCF10A cell line, which is an immortalised but non-transformed breast epithelial cell line without high endogenous ER expression.
Clones of MCF10A cells were characterised which stably overexpressed ERα (10A-ERα2, 10A-ERα13) or which stably overexpressed ERβ (10A-ERβ12, 10A-ERβ15). Overexpression of either ERα or ERβ allowed induction of an oestrogen-regulated ERE-LUC reporter gene by oestradiol which was not found in the untransfected cells. Oestradiol also increased proliferation of 10A-ERα13 and 10A-ERβ12 cells, but not untransfected cells, by 1.3-fold over 7 days. The phytoestrogen, genistein, which is reported to bind more strongly to ERβ than to ERα, could induce luciferase gene expression from an ERE-LUC reporter gene at concentrations of 10-6 M and 10-5 M but only in the clones overexpressing ERβ and not in those overexpressing ERα. Clone 10A-ERβ12 also yielded growth stimulation with 10-6 M genistein. Finally, the overexpression of ERα, but not ERβ, gave rise to increased growth in semi-solid methocel suspension culture in the presence of 70 nM oestradiol, suggesting that overexpression of ERα, but not ERβ, produces characteristics of a transformed phenotype.
This provides a model system to compare effects of oestradiol with other oestrogenic ligands in cells stably overexpressing individually ERα or ERβ.
Background:
Benign breast disease and high breast density are prevalent, strong risk factors for breast cancer. Women with both risk factors may be at very high risk.
Methods:
We included 42818 women participating in the Breast Cancer Surveillance Consortium who had no prior diagnosis of breast cancer and had undergone at least one benign breast biopsy and mammogram; 1359 women developed incident breast cancer in 6.1 years of follow-up (78.1% invasive, 21.9% ductal carcinoma in situ). We calculated hazard ratios (HRs) using Cox regression analysis. The referent group was women with nonproliferative changes and average density. All P values are two-sided.
Results:
Benign breast disease and breast density were independently associated with breast cancer. The combination of atypical hyperplasia and very high density was uncommon (0.6% of biopsies) but was associated with the highest risk for breast cancer (HR = 5.34; 95% confidence interval [CI] = 3.52 to 8.09, P < .001). Proliferative disease without atypia (25.6% of biopsies) was associated with elevated risk that varied little across levels of density: average (HR = 1.37; 95% CI = 1.11 to 1.69, P = .003), high (HR = 2.02; 95% CI = 1.68 to 2.44, P < .001), or very high (HR = 2.05; 95% CI = 1.54 to 2.72, P < .001). Low breast density (4.5% of biopsies) was associated with low risk (HRs <1) for all benign pathology diagnoses.
Conclusions:
Women with high breast density and proliferative benign breast disease are at very high risk for future breast cancer. Women with low breast density are at low risk, regardless of their benign pathologic diagnosis.
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.
Aluminium is a toxic metal whose genotoxicity has been scarcely studied in aquatic species and more generally in mammals. Recently, human and ecological disaster caused by the discharge of red mud in Hungary has revived questions about the toxicity of this metal particularly for the environment. On the contrary, cadmium is a highly toxic metal whose genotoxicity has been well characterized in various mammalian cells. However on non-human cells, little is known about its impact on DNA damage and repair. In this study, the genotoxic potential of both metals on embryonic zebrafish cells ZF4 was analyzed and particularly the impairment of the major DNA double strand breaks (DSB)-repair pathway, i.e. non-homologous end-joining (NHEJ). To this aim, DNA single strand breaks (SSB) and DSB were evaluated using the comet assay and the immunodetection of γ-H2AX proteins, respectively, in AlCl(3) or CdCl(2) exposed ZF4 cells. These exposures result in the production of DSBs a few hours after incubation. The DNA-PK kinase activity, essential for NHEJ, is more affected by the presence of aluminium than cadmium. Altogether our data provide evidence of the high toxicity induced by aluminium in zebrafish and indicates the pertinence of genotoxicity evaluation in organisms living in contaminated water.
The epithelial-mesenchymal transition (EMT) confers mesenchymal properties on epithelial cells and has been closely associated with the acquisition of aggressive traits by carcinoma cells. EMT programs are orchestrated by a set of pleiotropically acting transcription factors (TFs). The actions of these EMT-TFs enable the early steps of metastasis: local invasion and subsequent dissemination of carcinoma cells to distant sites. However, in most malignancies, the subsequent outgrowth of micrometastatic deposits into macroscopic metastases has the greatest impact on clinical progression. Such metastatic "colonization" reflects the ability of disseminated tumor cells to adapt to a foreign tissue microenvironment. The outgrowth of a metastasis is also thought to be associated with self-renewal, the defining cellular trait of cancer stem cells (CSCs), also termed tumor-initiating cells. Importantly, molecular links between EMT-TFs and self-renewal have emerged, suggesting that EMT programs play critical roles both early and late in the metastatic cascade. The genetic and epigenetic mechanisms that regulate the activation of EMT-TFs and the traits they induce are areas under intensive investigation. Such studies may provide new opportunities for therapeutic intervention and help to overcome tumor heterogeneity and therapeutic resistance.
This paper presents the latest international descriptive epidemiological data for invasive breast cancer amongst women, including incidence, survival and mortality, as well as information on mammographic screening programmes.
Almost 1.4 million women were diagnosed with breast cancer worldwide in 2008 and approximately 459,000 deaths were recorded. Incidence rates were much higher in more developed countries compared to less developed countries (71.7/100,000 and 29.3/100,000 respectively, adjusted to the World 2000 Standard Population) whereas the corresponding mortality rates were 17.1/100,000 and 11.8/100,000. Five-year relative survival estimates range from 12% in parts of Africa to almost 90% in the United States, Australia and Canada, with the differential linked to a combination of early detection, access to treatment services and cultural barriers. Observed improvements in breast cancer survival in more developed parts of the world over recent decades have been attributed to the introduction of population-based screening using mammography and the systemic use of adjuvant therapies.
The future worldwide breast cancer burden will be strongly influenced by large predicted rises in incidence throughout parts of Asia due to an increasingly "westernised" lifestyle. Efforts are underway to reduce the global disparities in survival for women with breast cancer using cost-effective interventions.
The aim of this study was to investigate the cadmium (Cd), nickel (Ni) and aluminium (Al) concentrations in female breast cancer and normal tissue.
The concentration of metals in 16 non-cancerous breast tissues and 67 breast cancer samples was measured by flame atomic absorption spectrometry.
In the case of normal breast tissue the concentrations were 0.61 ± 0.24 μg Cd/g dry tissue, 1.84 ± 0.67 μg Ni/g dry tissue, and 3.63 ± 1.00 μg Al/g dry tissue, whereas in breast cancer concentrations of metals were 0.76 ± 0.38 μg/g dry tissue, 2.26 ± 0.79 μg/g dry tissue, and 4.40 ± 1.82 μg/g dry tissue, respectively. The concentration of Cd and Al in normal breast tissue was significantly lower than in breast cancer. In the case of Ni concentration, we did not observe statistically significant differences between normal and cancerous tissue. There were no significant differences in concentration of studied metals, in breast cancer, in the context of age, menopausal status, and cancer histological grading.
The data obtained show higher concentration of cadmium and aluminium and support a possible relationship between those metals and breast cancer.
Aluminium salts used as antiperspirants have been incriminated as contributing to breast cancer incidence in Western societies. To date, very little or no epidemiological or experimental data confirm or infirm this hypothesis. We report here that in MCF-10A human mammary epithelial cells, a well-established normal human mammary epithelial cell model, long-term exposure to aluminium chloride (AlCl(3) ) concentrations of 10-300 µ m, i.e. up to 100 000-fold lower than those found in antiperspirants, and in the range of those recently measured in the human breast, results in loss of contact inhibition and anchorage-independent growth. These effects were preceded by an increase of DNA synthesis, DNA double strand breaks (DSBs), and senescence in proliferating cultures. AlCl(3) also induced DSBs and senescence in proliferating primary human mammary epithelial cells. In contrast, it had no similar effects on human keratinocytes or fibroblasts, and was not detectably mutagenic in bacteria. MCF-10A cells morphologically transformed by long-term exposure to AlCl(3) display strong upregulation of the p53/p21(Waf1) pathway, a key mediator of growth arrest and senescence. These results suggest that aluminium is not generically mutagenic, but similar to an activated oncogene, it induces proliferation stress, DSBs and senescence in normal mammary epithelial cells; and that long-term exposure to AlCl(3) generates and selects for cells able to bypass p53/p21(Waf1) -mediated cellular senescence. Our observations do not formally identify aluminium as a breast carcinogen, but challenge the safety ascribed to its widespread use in underarm cosmetics.
The pro-oxidant activity of aluminum, a nonredox metal, through superoxide formation is studied by theoretical methods, determining the ESR g-tensor values of O(2)(center dot-) with a variety of metals and the reaction energies for Al(3+) superoxide affinity in solution. First, the intrinsic ability of aluminum to induce a splitting of the pi(g) levels is compared to that of other significant biological metals, such as Na(+), K(+), Mg(2+), and Ca(2+). Additional properties such as bond lengths, ionization potentials, and electron affinities are also determined, and the coherency with the trends observed from ESR g-tensor values is analyzed. As it corresponds to the high charge and its small size, there is a strong interaction between Al(3+) and the superoxide. We predict that this strong inherent interaction remains when aluminum is microsolvated. Finally, we analyze the possibility of Al(3+) superoxide formation in solution, leading to the conclusion that substitution of the first coordination shell water molecules is plausible, but not of hydroxides. This points to the possibility of Al(3+) superoxide formation in solution, which would be pH-dependent. Taking into account the earlier established linear relationship between metal superoxide interactions and promoting effects in electron-transfer reactions, our work reinforces the idea that the presence of aluminum in biological systems could lead to an important pro-oxidant activity through a superoxide formation mechanism.
BRCA mutation-associated breast cancer differs from sporadic breast cancer with regard to future cancer risks and sensitivity to systemic therapies. Now that rapid genetic testing for BRCA1 and BRCA2 mutations is available at the time of breast cancer diagnosis, BRCA mutation status can be considered when making treatment and prevention decisions for BRCA mutation carriers with breast cancer. This article reviews surgical options for management of affected BRCA mutation carriers with emphasis on the risks of ipsilateral recurrence and contralateral breast cancer. The roles of breast-conserving surgery, prophylactic mastectomy, and oophorectomy are reviewed. In addition, the sensitivity of BRCA mutation-associated breast cancer to endocrine therapy, platinum chemotherapy, and poly (ADP-ribose) polymerase inhibitors is reviewed.
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.
Throughout the latter half of the 20th century, hormone-replacement therapy (HRT) use steadily increased in the Western world. In 2002, the early termination of the Women's Health Initiative trial due to an excess of adverse events attributable to HRT, led to a precipitous decline in its use. Breast cancer incidence began to decline soon thereafter in the USA and several other countries. However, the magnitude of the decline in breast cancer incidence, and its timing with respect to HRT cessation, shows considerable variability between nations. The impact of HRT cessation appears most significant and immediate in countries with the largest absolute decline in HRT use. In countries in which peak prevalence of HRT use was high, several studies have convincingly excluded decreasing rates of mammographic screening as an explanation for the decline in breast cancer incidence. Conversely, in some countries, no decline in breast cancer incidence is apparent that can be readily attributed to declining trends in HRT use. In such cases, declines in breast cancer incidence may be related instead to saturation or decreased utilisation of mammographic screening programmes. In other cases, it is difficult to disentangle the respective influence of trends in HRT use, and the influence of changes relating to mammographic screening. However, irrespective of time lags and varying magnitudes of effect, the data convincingly support a direct association between decreasing HRT use and declining breast cancer incidence.
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.
This paper reviews the recent scientific literature on PCDDs, PCDFs and dioxin-like PCBs in human milk. All the papers reporting levels of these contaminants in human breast milk published from January 2000 to January 2009 and available on the www.sciencedirect.com web site were identified and included. The aim was (1) to study levels of PCDDs, PCDFs and PCBs in human milk in mothers from different geographical areas and assess infant exposure to these contaminants; (2) to study the effect of variables such as the mother's age, number of deliveries, dietary and smoking habits and her own nutrition in infancy, and the environment, on levels of the contaminants in breast milk; (3) to study time patterns, and (4) to identify data gaps.
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.
Breast cancer is a worldwide problem affecting more than 1 million women annually. Currently, best care for women with breast cancer involves a multidisciplinary approach requiring a broad understanding of epidemiologic, genetic, prognostic, and predictive factors. This study will discuss the epidemiology and risk factors associated with breast cancer.
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.
Analysis of nipple aspirate fluid (NAF) allows the noninvasive identification of both cellular and biomolecular markers of human breast cancer, the most common female malignancy in developed countries. Cytosolic superoxide dismutase (SOD-1) represents a detoxifying enzyme able to regulate the balance between oncogenic and oncosuppressor reactive oxygen species.
We analyzed SOD-1 expression in 126 NAF samples collected from 67 women with and 59 without breast cancer, using enzyme-linked immunosorbent assay, immunoprecipitation, Western blotting, and immunocytochemistry.
SOD-1 median values in plasma presented no difference between the no-cancer and cancer subgroups. No significant difference in the median level of SOD-1 between matched plasma and NAF from cancer patients was found, whereas SOD-1 median level in no-cancer NAF was significantly higher when compared with matched plasma. Finally, the SOD-1 median value in no-cancer NAF was significantly higher (about 2-fold) than in cancer NAF.
NAF measurement of SOD-1 is a useful tool to identify intracellular redox status of the breast microenvironment, mirroring the oxidative metabolic pathways occurring in breast tissue, both in physiologic and cancer conditions and in improving the identification of women at increased breast cancer risk. SOD-1 activity in the breast microenvironment may represent a functional "switch" between the detrimental/oncogenic properties and the oncosuppressor/proapoptotic role of this antioxidant enzyme.
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.
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.
The rumor that antiperspirant use causes breast cancer continues to circulate the Internet. Although unfounded, there have
been no published epidemiologic studies to support or refute this claim. This population-based case– control study investigated
a possible relationship between use of products applied for underarm perspiration and the risk for breast cancer in women
aged 20–74 years. Case patients (n = 813) were diagnosed between November 1992 and March 1995; control subjects (n = 793)
were identified by random digit dialing and were frequency-matched by 5-year age groups. Product use information was obtained
during an in-person interview. Odds ratios (ORs) and 95% confidence intervals were estimated by the use of conditional logistic
regression. P values were determined with the Wald χ2 test. All statistical tests were two-sided. The risk for breast cancer did not increase with any of the following activities:
1) antiperspirant (OR = 0.9; P = .23) or deodorant (OR = 1.2; P = .19) use; 2) product use among subjects who shaved with a blade razor; or 3) application of products within 1 hour of shaving
(for antiperspirant, OR = 0.9 and P = .40; for deodorant, OR = 1.2 and P = .16). These findings do not support the hypothesis that antiperspirant use increases the risk for breast cancer.
The elaboration of biogeochemical cycles for elements which are known to be essential for life has enabled a broad appreciation of the homeostatic mechanisms which underlie element essentiality. In particular they can be used effectively to identify any part played by human activities in element cycling and to predict how such activities might impact upon the lithospheric and biospheric availability of an element in the future. The same criteria were the driving force behind the construction of a biogeochemical cycle for aluminium, a non-essential element which is a known ecotoxicant and a suspected health risk in humans. The purpose of this exercise was to examine the concept of a biogeochemical cycle for aluminium and not to review the biogeochemistry of this element. The cycle as presented is rudimentary and qualitative though, even in this nascent form, it is informative and predictive and, for these reasons alone, it is deserving of future quantification. A fully fledged biogeochemical cycle for aluminium should explain the biospheric abundance of this element and whether we should expect its (continued) active involvement in biochemical evolution.
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.
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.