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Aluminium and breast cancer: Sources of exposure, tissue measurements and mechanisms of toxicological actions on breast biology
... However, environmental factors should not be neglected (Linhart et al., 2017;McGrath, 2003). Due to the high incidence of breast cancer in the upper outer quadrant (Darbre, 2009;Linhart et al., 2017;Pineau et al., 2014), the underarm area's cosmetic products are introduced as a risk factor (Darbre, 2009;Darbre, Mannello, & Exley, 2013;Linhart et al., 2017;Pineau et al., 2014). ...
... The unwanted oestrogenic effects of aluminium, such as altered protein expression, change in puberty signs and tumour development, may be seen (House et al., 2013;Mandriota et al., 2016;Mannello et al., 2013;Pineau et al., 2014;Rodrigues-Peres et al., 2013a, 2013bWallace, 2015). Overall metalloestrogenic effects of aluminium may potentiate the breast's changes (Darbre, 2009;Darbre, Mannello, & Exley, 2013;Wallace, 2015). Defatted breast tissue (Mulay et al., 1971) 3.75 ppm dry tissue Total breast tissue (Ng et al., 1997) 22.16 ± 1.83 μg/g dry weight Total breast tissue (Pasha et al., 2008) 8.94 μg/g ...
... nmol/g 3.8, 2.5-5.8 nmol/g Breast tissue fat 3-192 nmol/g oil Breast biopsy (Darbre, Mannello, & Exley, 2013) 82.8 μg/g (range 12. (Linhart et al., 2017). Table 5. ...
Usage of inorganic ingredients like aluminium salts in cosmetics and personal care products has been a concern for producers and consumers. Although aluminium is used to treat hyperhidrosis, some worries have been raised about aluminium's role in breast cancer, breast cyst and Alzheimer's disease. The human population is exposed to aluminium from vaccines, diet, and drinking water, but the frequent use of aluminium‐based cosmetics might add additional local exposure. This paper reviews literature to determine if aluminium‐based products may pose potential harm to the body. The dermal absorption of aluminium is not widely understood. It is not yet known whether aluminium can travel from the skin to brain to cause Alzheimer's disease. Aluminium may cause gene instability, alter gene expression or enhance oxidative stress, but the carcinogenicity of aluminium has not been proved yet. Until now, epidemiological researches were based on oral information, which lacks consistency, and the results are conflicting. Future studies should target real‐life‐based long‐time exposure to antiperspirants and other aluminium‐containing cosmetics and personal care products. The usage of aluminium salts in cosmetics and personal care products has been a matter of concern for producers and consumers. It has been found that there is not any clear consensus on the potential harm of aluminium‐based products. The epidemiological studies are not enough. The rate of absorption of aluminium through the skin is not clear. Further real‐life and long‐time exposure‐based studies are needed.
... 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.
... 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.
... 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.
... Food intake and PCP utilization are considered the most important sources of human exposure to Al (Sanajou et al., 2021;Sander et al., 2018;Wong et al., 2010), which is known to be a neurotoxic metal with estrogenic and genotoxic potential (Darbre, 2006;Exley, 2014). Human exposure to Al has been associated with Parkinson disease and other neurodegenerative disorders (Ullah et al., 2021) as well as breast cancer (Darbre et al., 2013). The few studies on Al concentrations in breast milk (Chao et al., 2014;Mannello et al., 2009;Taravati Javad et al., 2018) have included two investigations in Spain (Fernandez-Lorenzo et al., 1999;Motas et al., 2021). ...
Aluminum (Al), antimony (Sb), and lithium (Li) are relatively common toxic metal(oid)s that can be transferred into breast milk and potentially to the nursing infant. This study assessed concentrations of Al, Sb, and Li in breast milk samples collected from donor mothers and explored the predictors of these concentrations. Two hundred forty-two pooled breast milk samples were collected at different times post-partum from 83 donors in Spain (2015-2018) and analyzed for Al, Sb, and Li concentrations. Mixed-effect linear regression was used to investigate the association of breast milk concentrations of these elements with the sociodemographic profile of the women, their dietary habits and utilization of personal care products (PCPs), the post-partum interval, and the nutritional characteristics of milk samples, among other factors. Al was detected in 94% of samples, with a median concentration of 57.63 μg/L. Sb and Li were detected in 72% and 79% of samples at median concentrations of 0.08 μg/L and 0.58 μg/L, respectively. Concentrations of Al, Sb, and Li were not associated with post-partum time. Al was positively associated with total lipid content of samples, weight change since before pregnancy, and coffee and butter intakes and inversely with meat intake. Li was positively associated with intake of chocolate and use of face cream and eyeliner and inversely with year of sample collection, egg, bread, and pasta intakes, and use of hand cream. Sb was positively associated with fatty fish, yoghurt, rice, and deep-fried food intakes and use of eyeliner and inversely with egg and cereal intakes and use of eyeshadow. This study shows that Al, Sb, and Li, especially Al, are widely present in donor breast milk samples. Their concentrations in the milk samples were most frequently associated with dietary habits but also with the lipid content of samples and the use of certain PCPs.
... Les niveaux d'Al dans les tissus mammaires étaient significativement plus élevés dans les cas de cancer du sein que dans les témoins (5,8 contre 3,8 nmol.g -1 ). En plus, les patientes atteintes d'un cancer du sein présentaient des taux d'Al plus élevés dans les tissus mammaires que dans le sérum sanguin (Darbre et al., 2013). Bien qu'il existe un lien entre l'utilisation de produits cosmétiques pour aisselles et l'incidence du cancer du sein, il n'est pas toujours facile de mettre un mécanisme à ce lien (Darbre, 2016). ...
Omniprésent dans notre vie quotidienne, l’aluminium (Al) est l’un des éléments traces métalliques les plus dangereux pour la santé humaine. Nous y sommes exposés quotidiennement, par l’alimentation, l’application d’antitranspirants, l’utilisation d’antiacides, la vaccination, etc. L’exposition est donc inévitable, et chaque jour des taux modérés de ce métal pénètrent dans l’organisme et sont capables de s’accumuler dans certains organes. Malgré cela, la majorité de la population humaine n’est pas à risque évident de toxicité aluminique, puisque notre corps est équipé de plusieurs mécanismes qui ne permettent pas une absorption et une accumulation faciles, et facilitent son élimination. Par conséquent, une très faible quantité d’Al atteindra les différents organes et tissus (poumons, foie, cerveau, etc.). Une exposition élevée à l’Al entraîne des effets toxiques pulmonaires, gastro-intestinaux, cardiovasculaires, hématologiques, musculosquelettiques, neurologiques, hépatopancréatiques, etc. Les populations les plus exposées sont les patients dialysés, les consommateurs d’antiacides à long terme, et les professionnels de l’Al.
... The potential systemic toxicity of aluminum-based antiperspirants via dermal application has been a matter of concern over the years as several studies have implicated these products as contributory factors in the development of breast cancer and neurodegenerative diseases (e.g., Alzheimer's disease) (Darbre et al., 2011(Darbre et al., , 2013Exley et al., 2007;Farasani & Darbre, 2015;Linhart et al., 2017;Sappino et al., 2012). However, aluminum salts have shown to be poorly absorbed through the skin and the daily use of aluminum-based antiperspirants is not believed to contribute to systemic exposure. ...
Aluminum chlorohydrate (ACH) is a major aerosol component frequently used as the active ingredient in antiperspirants, and in vivo studies have raised a concern about its inhalation toxicity. Still, few studies have addressed its effects on the human respiratory tract. Therefore, we developed a study on ACH inhalation toxicity using an in vitro human alveolar cell model (A549 cells) with molecular and cellular markers of oxidative stress, immunotoxicity, and epigenetic changes. The chemical characterization of ACH suspensions indicated particle instability and aggregation; however, side‐scatter analysis demonstrated significant particle uptake in cells exposed to ACH. Exposure of A549 cells to non‐cytotoxic concentrations of ACH (0.25, 0.5 and 1 mg/mL) showed that ACH induced reactive oxygen species. Moreover, ACH upregulated TNF, IL6, IL8 and IL1A genes, but not the lncRNAs NEAT1 and MALAT1. Finally, no alterations on the global DNA methylation pattern (5‐methylcytosine and 5‐hydroxymethylcytosine) or the phosphorylation of histone H2AX (γ‐H2AX) were observed. Our data suggest that ACH may induce oxidative stress and inflammation on alveolar cells, and A549 cells may be useful to identify cellular and molecular events that may be associated with adverse effects on the lungs. Still, further research is needed to ensure the inhalation safety of ACH. Aluminum chlorohydrate (ACH) is an aerosol component used in antiperspirants, but its effects in the human respiratory tract are unclear. A549 cells were used as an in vitro cell model to investigate ACH lung toxicity. Despite instability and aggregation, ACH particle uptake was observed in A549 cells. Our results shows that ACH can increase reactive oxygen species and TNF, IL6, IL8 and IL1A mRNA in A549 cells. Our data may direct future research on the potential inhalation toxicity of ACH.
... Further, Aluminium is also reported to increase the rate of ROS production, glutathione depletion and mitochondrial dehydrogenase activity in cells of glial origin [8]. Aluminium has also been found to be deposited at higher concentration in breast tissues in patients suffering from breast cancer and has been implicated to the use of aluminium based antiperspirants [9,10]. ...
Aluminium ions play an important role in various biological processes and the development of methods for its detection has received significant attention recently. Among the reported analytical methods for aluminium ions, fluorescence based detection is considered very advantageous because of its extreme sensitivity and simplicity. However, a large majority of these reported sensor systems for aluminium detection are either based on synthetically involved fluoregenic probes or perform sensing operation via single wavelength based response which makes them susceptible to error due to minute variation in analyte-independent experimental variables. Thus, in the present contribution, we describe a fluorescence ratiometric sensor for the sensitive and selective detection of Al³⁺ which is based on Al³⁺ ion dependent modulation of aggregate-monomer equilibrium of Thioflavin-T-Polyacrylic acid system. The molecular rotor dye, Thioflavin-T (ThT), undergoes efficient aggregation, with a distinct emission band, in the presence of a carboxyl laced polyelectrolyte, poly (acrylic acid), PAA. This ThT-PAA monomer-aggregate system undergoes significant modulation in the presence of Al³⁺ ion due to selective interaction of hard Al³⁺ ions with hard donors like oxygen containing carboxylate groups. This modulation provides a fluorescence ratiometric response for Al³⁺ originating from distinct spectroscopic features of ThT monomers and aggregates. Overall, the sensor system provides a selective and sensitive response towards detection of Al³⁺ with a LOD of 0.8 μM. Importantly, the sensor system is composed of commercially available components and provides freedom from the reliance on time-consuming and tedious protocols required for producing the probe molecules. The ratiometric response provides a robustness to the analytical performance as compared to the system that operates through single wavelength based measurements. We have also demonstrated the sensor system response in real water samples from tap water.
... It was found that the elevation in concentrations of various transition metal ions, mainly Fe +3 , Cu 2+ , and Zn 2+ , occurred in senile plaques [70]. Furthermore, from the past few years, there is an increasing interest in aluminum due to its association as a cause for breast cancer as because of its use as an antiperspirant agent from quite a long time in underarm cosmetics [71][72][73]. Therefore, metal-based drugs with enhanced biological activities acting either as chemotherapeutic or diagnostic agents nowadays. ...
Hydroxypyridinones (HOPOs) are excellent class of chelators that have been gaining attention in the field of pharmaceutical drugs by their high chelating efficacy and specificity with different metal ions. Among all the metal ions, they exhibit a high binding affinity towards iron (III) and are clinically used as iron chelators nowadays. The HOPO family has different isomers, out of which 3,4-HOPO possesses applicability for designing drugs. The effect of methyl substitution on different positions of pyridinone ring also plays an essential role in deciding the pM values, thus describing the metal affinity. Several metal ions like Fe, Al, Cu, Zn, and some actinides are found to exhibit good chelation efficacy with HOPOs. In terms of denticity, there are various forms of HOPO. Among these, discussion on bidentate, tetradentate, hexadentate, octadentate, and dendrimers will be done here. This review systematically summarizes the various literature reports on the design and pharmacological activities of the newly developed HOPOs and their derivatives, including antibiotics, anticancer, and antineurodegeneratives.
... Most of his studies were observational, but he also performed an interventional study by investigating the levels of urokinase-type plasminogen activator (uPa) in NAF after oral administration of colecoxib, a non-steroidal anti-inflammatory drug [101]. He also wrote four reviews summarizing current knowledge about proteins, hormones and aluminum detected in NAF of breast cancer patients compared to healthy controls [47,[102][103][104]. His latest publication was a comment reflecting on the potential of investigating biomarkers in NAF [105]. ...
Nipple aspirate fluid (NAF) is an intraductal mammary fluid that, because of its close proximity to and origin from the tissue from which breast cancer originates, is a promising source of biomarkers for early breast cancer detection. NAF can be non-invasively acquired via the nipple by aspiration using a suction device; using oxytocin nasal spray helps increase yield and tolerability. The aspiration procedure is generally experienced as more tolerable than the currently used breast imaging techniques mammography and breast magnetic resonance imaging. Future applications of NAF-derived biomarkers include their use as a tool in the detection of breast carcinogenesis at its earliest stage (before a tumor mass can be seen by imaging), or as a supporting diagnostic tool for imaging, such as when imaging is less reliable (to rule out false positives from imaging) or when imaging is not advisable (such as during pregnancy and breastfeeding). Ongoing clinical studies using NAF samples will likely shed light on NAF’s content and clinical potential. Here, we present a narrative review and perspectives of NAF research at a glance.
... 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.
... 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.
... 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.
... 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.
... 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.
... 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.
... 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 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.
... 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
... 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.
... 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.
... 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.
... 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.
... 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.
... 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.
... 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, 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.
... 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.
... 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.
... 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.
An AIE (aggregation induced emission) active probe DFP-AMQ was designed and synthesized as a hexa-coordinated N2O donor chelator for the selective sensing of Al3+ colorimetrically as well as fluorimetrically with a 27-fold fluorescence enhancement for CH3CN-H2O (9 : 1, v/v, pH 7.2, HEPES buffer). The fluorescence enhancement occurred through the blocking of ESIPT, chelation enhanced fluorescence effect (CHEF) arose, and as a result fluorescence enhancement was observed through 1 : 1 complexation with Al3+ ions. Detailed spectroscopic studies including UV-Vis, FTIR, 1H NMR, and HRMS studies were carried out to characterize the probable structure of DFP-AMQ including the complexation of DFP-AMQ with Al3+ ions. The spectrophotometric and spectrofluorimetric titrations revealed strong binding towards Al3+ and the K d values were obtained from UV-Vis (3.26 × 10-5 M-1) and fluorescence titration (2.02 × 10-5 M-1). The limit of detection of Al3+ by DFP-AMQ was 1.11 μM. The quantum yields of DFP-AMQ and [DFP-AMQ-Al]+ were calculated to be 0.008 and 0.211, respectively. Dynamic light scattering (DLS) studies showed that the sizes of the particles increased with increasing water percentage due to aggregation. SEM (scanning electron microscopy) studies revealed interesting morphological changes in microstructures in which DFP-AMQ demonstrated a rod-like shape, which was converted to a spherical-like shape in the presence of Al3+ and when DFP-AMQ aggregated in H2O it showed aggregated block-like shape. In the solid phase, DFP-AMQ with nitrate has no particular shape, but in the presence of acetate, it converts to stone-like shape. This probe (DFP-AMQ) could be employed for on-site Al3+ ion detection in the solid state.
A hydrazine derived Bis(2-hydroxybenzylidene)-[1,1'-biphenyl]-2,2'-dicarbohydrazide (sensor 1) has been synthesized and its sensing properties towards metal ions has been demonstrated using simple UV-visble spectroscopic, fluorometric technique and visible colour change. The...
Certain environmental contaminants such as heavy metals, pesticides, and mycotoxins are presumed to play a crucial role in the etiology of breast cancer, which is the most common tumor in women worldwide. In fact, the exposure to heavy metals poses risk in causing human cancers. Several investigations indicated strong contribution of heavy metals especially copper, arsenic, zinc, cadmium, lead, and aluminum in breast cancer. Furthermore, it has been reported that the excessive use of pesticides in agriculture in order to improve the productivity contaminates food materials and can be responsible to induce breast cancer in women. It is also noted that some fungi produce several type of mycotoxins such us zearalenone, aflatoxin, and ochratoxin that are dangerous for human health and can especially cause breast cancer. Thus, the objective of this chapter is to discuss the experimental data regarding the involvement of heavy metals, pesticides, and mycotoxins as well as the recent insights on the molecular mechanisms involved in the progress of breast cancer.
This chapter provides an overview of the chemical components of personal care products (PCPs) that possess endocrine-disrupting activity and cites evidence that such endocrine-disrupting chemicals (EDCs) can be absorbed from application to human skin. Reported cases are described where absorption of EDCs from PCPs has affected human endocrine health. The use of PCPs presents high dermal exposure to multiple EDCs on a daily basis, and many of these EDCs have been measured in human tissue. Although it is not possible to identify the source of each EDC measured in human tissue, many of these chemicals are used only in PCPs, and several studies have found an association between concentrations measured in the tissue and self-reported use of PCPs. Dermal application of PCPs as a source of EDCs is an emerging issue, and national and international regulatory bodies are moving toward greater regulation of the component chemicals.
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.
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.
Drinking-water plants often use aluminium (Al) salts as coagulant agents in the water-treatment process, which cause increasing aluminum residue levels in water. Aluminum accumulation in the human body has been related to neurological disorders such as Alzheimer's disease, senile dementia and breast cancer. This work utilises the available industrial waste as a cheap source of carbon (C) that can be used in aluminium ion elimination from water supplies. The employed sugarcane bagasse activated carbon (SCB-AC) was derived from the waste of a Qus sugar factory in Qena City, Egypt. The activity of SCB-AC was compared with that of commercial activated carbon (Com-AC), and their physico-chemical properties were characterised by various techniques (energy-dispersive X-ray spectroscopy, scanning electron microscopy and Fourier transform infrared spectroscopy). The findings demonstrate that SCB-AC has high performance for aluminium (III) (Al3+) removal like Com-AC, which reached 80% at a high initial concentration (10 mg/l). The thermodynamic constants revealed that the adsorption process has an exothermic nature. Briefly, SCB-AC is an inexpensive eco-friendly carbon with an excellent adsorptive ability like that of Com-AC for elimination of aluminium (III) in drinking water. The cost of manufacturing SBC-AC would be about US$40/t.
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.
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).
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.
/
________________________________________
Keywords:
SCCS, scientific opinion, Aluminium, Regulation 1223/2009
________________________________________
Opinion to be cited as:
SCCS (Scientific Committee on Consumer Safety), Opinion on the safety of aluminium in cosmetic products, preliminary version of 30-31 October 2019, final version of 03-04 March 2020, SCCS/1613/19.
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.
(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.
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.
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...
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.
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.
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.
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.
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.
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.
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.
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.