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Aluminium and the human breast
Abstract
The human population is exposed to aluminium (Al) from diet, antacids and vaccine adjuvants, but frequent application of Al-based salts to the underarm as antiperspirant adds a high additional exposure directly to the local area of the human breast. Coincidentally the upper outer quadrant of the breast is where there is also a disproportionately high incidence of breast cysts and breast cancer. Al has been measured in human breast tissues/fluids at higher levels than in blood, and experimental evidence suggests that at physiologically relevant concentrations, Al can adversely impact on human breast epithelial cell biology. Gross cystic breast disease is the most common benign disorder of the breast and evidence is presented that Al may be a causative factor in formation of breast cysts. Evidence is also reviewed that Al can enable the development of multiple hallmarks associated with cancer in breast cells, in particular that it can cause genomic instability and inappropriate proliferation in human breast epithelial cells, and can increase migration and invasion of human breast cancer cells. In addition, Al is a metalloestrogen and oestrogen is a risk factor for breast cancer known to influence multiple hallmarks. The microenvironment is established as another determinant of breast cancer development and Al has been shown to cause adverse alterations to the breast microenvironment. If current usage patterns of Al-based antiperspirant salts contribute to causation of breast cysts and breast cancer, then reduction in exposure would offer a strategy for prevention, and regulatory review is now justified.
... During our lifetime we are therefore chronically exposed to aluminium through the digestive, dermic, and respiratory routes. The aluminium we absorb reaches relatively high concentrations in the bone, the liver, and the mammary gland (1,3). ...
... These data do not seem to reassure regarding the amounts of aluminium we are exposed to daily, as witnessed by the numerous publications dealing with potential toxic effects of our daily exposure to aluminium and by the many, regularly updated aluminium safety assessment reports emanating from industries and governmental bodies. Low level, chronic exposure to aluminium has long been suspected of being involved in at least two human pathologies: Alzheimer disease (8) and cancer (3,9). The former link is not consistently supported by existing epidemiological data (10). ...
... First, they provide one likely mechanism for the transforming effects of aluminium. Second, like cellular transformation, chromosomal instability occurred in cells exposed to aluminium concentrations close to those measured in the mammary gland of women living in industrialized countries (3). Third, our results in mammary epithelial cells were confirmed and extended in V79 cells, a wellrecognized model for the assessment of chemical carcinogens in human toxicology (41). ...
Because of its chemical versatility and abundance in nature, aluminium is employed in a myriad of frequently used products - including cosmetics and food additives - and applications – drinking water purification procedures being an example. Despite what its widespread use might suggest, aluminium’s harmlessness is a matter of debate in the scientific community. In this article we trace the lines of a growing questioning about the potential mutagenic effects of this metal, due to the data produced over the recent years, and with an eye to the discussions currently underway in this regard between the scientific community, industry, and regulatory bodies.
... The human body is exposed to cosmetics and personal care products that contain aluminium salts daily. It has been hypothesized that aluminium in these products may harm human health; therefore, it should be removed from cosmetics and personal care products (Darbre, 2016;Fakri et al., 2006;Flarend et al., 2001;Rodrigues-Peres et al., 2013a, 2013b. However, antiperspirants are still prescribed in hyperhidrosis (HH) treatment (Brown et al., 2014;Hosp & Hamm, 2017). ...
... Breast and underarm area and around them are exposed to different cosmetic products like antiperspirants, deodorants and breast firming products once a day or even more. Most of the time, these products did not wash away and are left on the skin for days; continuous exposure increases the absorption rate and accumulation of cosmetic products into the skin (Darbre, 2016). The absorption rate may also increase by shaving those areas because of skin irritation and scratches. ...
... Therefore, there is a concern regarding the increased absorption rate of aluminium salts through broken skin (Zakaria & Ho, 2015 (Darbre, 2016). The concentration of aluminium in the nipple aspirate has been measured too. ...
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.
... Aluminum is unique based upon the various mechanisms of action whereby it is listed based on its carcinogenic activity. More often, human exposure to aluminum is the result of contamination of food, interestingly in the process of manufacturing vaccines for human use, and when added as a chemical salt during a variety of processes used in industry for manufactured products for commercial purposes [1,2]. The commercial products most susceptible are those in which aluminum salts are included in the list of added ingredients such as antacid tablets and antiperspirant deodorants [1][2][3]. ...
... More often, human exposure to aluminum is the result of contamination of food, interestingly in the process of manufacturing vaccines for human use, and when added as a chemical salt during a variety of processes used in industry for manufactured products for commercial purposes [1,2]. The commercial products most susceptible are those in which aluminum salts are included in the list of added ingredients such as antacid tablets and antiperspirant deodorants [1][2][3]. ...
... Experimental studies performed in mice exposed to AlCl 3 , which interestingly is the identical form of aluminum used in the manufacture of antiperspirant deodorants for humans, demonstrated an induction of malignant transformation of epithelial cells located within mammary glands [1]. Similar results were observed following exposure to human breast tissue epithelial cells [1][2][3]. Aluminum has been implicated in the development of neoplasia, specifically in the development of sarcomas [4]. In the same report it was noted that one patient, following consistent chronic exposure to aluminum, developed an atypical transformation resulting in a neuroectodermal malignancy [4]. ...
There has been increased concern on many levels focused on the environmental and occupational exposure of heavy metals and their impact on disease, specifically the carcinogenic potential inducing cancer in humans. Because the impact of heavy metals on human health continues to be a major health concern, research continues to improve our understanding of the carcinogenic potential of these substances. Of particular concern have been human exposure to aluminum, arsenic, beryllium, cadmium, lead, mercury, nickel, and radium and their carcinogenic potential whether contact is via environmental or occupational exposure. This updated review focuses on the carcinogenic mechanisms heavy metals use to induce malignant transformation of cells as well as addressing the overall environmental and occupational hazards of heavy metal exposure.
... Concentrations of aluminium in the range of those measured in the breast of women living in industrialized countries (0.8-87 µM) (reviewed in [6]) transform MCF-10A human mammary epithelial cells and NMuMG mouse mammary epithelial cells in vitro [7,8]. When injected into NOD-SCID or nude mice, NMuMG cells transformed in vitro by aluminium form tumours and metastasis [8]. ...
... We previously reported that long-term culture in the presence of 10-300 µM AlCl 3 transforms MCF10A human mammary epithelial cells or NMuMG mouse mammary epithelial cells [7,8]. The 10-300 µM concentration range overlaps with the aluminium content measured in the human mammary gland of women living in industrialized countries (0.8-87 µM) [6]. Chlorides of gallium or indium that, as aluminium, belong to the thirteenth group of the Mendeleev Table and hence have similar chemical properties had no effect [7]. ...
... In an attempt to distinguish between these two possibilities, following a short-24 h-incubation in the presence of AlCl 3 100 µM, or the same dilution (1/1000) of solvent (H 2 O) alone as a control, DAPI-stained metaphases of HC11 or NMuMG parental cells were inspected blind for the presence of chromosomal abnormalities: DSB, radials, chromosome fragmentation, premature chromosome condensation (PCC), telofusion, and premature chromatid separation. We selected this concentration of AlCl 3 because of its capacity to consistently induce mammary epithelial cell transformation in vitro ( [7,8]; this paper), and because of its proximity to the aluminium concentration range measured in the mammary gland of women living in industrialized countries (0.8-87 µM) [6]. In 24-h incubations, AlCl 3 increased the fraction of cells containing chromosomal structural abnormalities in HC11 cells, which carry a double p53 mutation [18], by approximately two-fold, compared to the controls. ...
Genomic instability is generally considered as a hallmark of tumorigenesis and a prerequisite condition for malignant transformation. Aluminium salts are suspected environmental carcinogens that transform mammary epithelial cells in vitro through unknown mechanisms. We report here that long-term culture in the presence of aluminium chloride (AlCl3) enables HC11 normal mouse mammary epithelial cells to form tumours and metastases when injected into the syngeneic and immunocompetent BALB/cByJ strain. We demonstrate that AlCl3 rapidly increases chromosomal structural abnormalities in mammary epithelial cells, while we failed to detect direct modulation of specific mRNA pathways. Our observations provide evidence that clastogenic activity—a well-recognized inducer of genomic instability—might account in part for the transforming abilities of aluminium in mammary epithelial cells.
... Toxicosis due to Al accumulation in mammalian tissues was associated with various pathologic effects (Wills and Savory, 1983;Kaiser et al., 1984;Boyce et al., 1986;Drüeke et al., 1986;Hewitt et al., 1990;Bushinsky et al., 1995;Reinke et al., 2003;Abubakar et al., 2004;Bogdanović et al., 2008;Yousef and Salama, 2009;Khattab et al., 2010;Blaylock, 2012;Buraimoh and Ojo, 2013;Sumathi et al., 2013). Recent reviews on toxic effects of Al covered reproductive toxicity (Mouro et al., 2017), pulmonary lesions (Kongerud and Søyseth, 2014;Taiwo, 2014), impact on the breast (Darbre, 2016), bone abnormalities (Chappard et al., 2016;Klein, 2019), immunotoxity (Zhu et al., 2014a) and neurologic disorders (Colomina and Peris-Sampedro, 2017;Morris et al., 2017). This review is an abridged and global overview of toxic effects of Al and its compounds, covering some relevant aspects of exposure and updated systemic toxicosis in humans and animals, relevant as background for prospective toxicopathologic studies. ...
... The proliferative and migratory characteristics of the human breast cancer cell may be affected by Al when it acts as a metalloestrogen or increases the intracellular secretion of matrix metalloproteinase (MMP9) and levels of activated MMP14 that are involved in migratory and invasive properties of cancerous cells, thereby influencing the metastatic process (Darbre et al., 2013a, b;Bakir and Darbre, 2015;Darbre, 2016). It is unclear whether Al has the capacity to initiate and promote any other carcinogenic process apart from the indirect evidence provided above with regard to breast cancer. ...
... Breast cancers and cysts are mammary gland conditions where emerging evidence are suggesting that Al may be involved in their causation (Darbre, 2016). Al chlorohydrate in antiperspirant cosmetics and other underarm cosmetic products may be an important source of Al exposure (Pineau et al., 2014;Linhart et al., 2017). ...
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.
... Toxicosis due to Al accumulation in mammalian tissues was associated with various pathologic effects (Wills and Savory, 1983;Kaiser et al., 1984;Boyce et al., 1986;Drüeke et al., 1986;Hewitt et al., 1990;Bushinsky et al., 1995;Reinke et al., 2003;Abubakar et al., 2004;Bogdanović et al., 2008;Yousef and Salama, 2009;Khattab et al., 2010;Blaylock, 2012;Buraimoh and Ojo, 2013;Sumathi et al., 2013). Recent reviews on toxic effects of Al covered reproductive toxicity (Mouro et al., 2017), pulmonary lesions (Kongerud and Søyseth, 2014;Taiwo, 2014), impact on the breast (Darbre, 2016), bone abnormalities (Chappard et al., 2016;Klein, 2019), immunotoxity (Zhu et al., 2014a) and neurologic disorders (Colomina and Peris-Sampedro, 2017;Morris et al., 2017). This review is an abridged and global overview of toxic effects of Al and its compounds, covering some relevant aspects of exposure and updated systemic toxicosis in humans and animals, relevant as background for prospective toxicopathologic studies. ...
... The proliferative and migratory characteristics of the human breast cancer cell may be affected by Al when it acts as a metalloestrogen or increases the intracellular secretion of matrix metalloproteinase (MMP9) and levels of activated MMP14 that are involved in migratory and invasive properties of cancerous cells, thereby influencing the metastatic process (Darbre et al., 2013a, b;Bakir and Darbre, 2015;Darbre, 2016). It is unclear whether Al has the capacity to initiate and promote any other carcinogenic process apart from the indirect evidence provided above with regard to breast cancer. ...
... Breast cancers and cysts are mammary gland conditions where emerging evidence are suggesting that Al may be involved in their causation (Darbre, 2016). Al chlorohydrate in antiperspirant cosmetics and other underarm cosmetic products may be an important source of Al exposure (Pineau et al., 2014;Linhart et al., 2017). ...
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.
... Mice subjected to the same type of aluminum salt exposed to antiperspirants develop breast cancerous cells. Related effects were found in tests of human breast cell cultures [1][2][3]. It is also speculated that heavy metals have a role in sarcomas [4]. ...
... Nickel hydroxide is suitable for systems; which nickel amounts are unsafe. It was observed that CaNa [2] EDTA recovers brain damage from nickel chloride, and eliminates nickel from Cirrhinus mrigala [90]. ...
There has been a growing recognition regarding heavy metal toxicity owing to their position in cancer induction. The study is linked to heavy metals like titanium, arsenic, beryllium, cadmium, lead, mercury, nickel and radium. A meta-analysis was compiled using PubMed to determine existing exposure channels, forms of cancers caused, and treatment interventions for the metals. It was planned to lead potential study activities linked to heavy metals and cancer.
... Les lésions hépatiques et pancréatiques provoquent des modifications du métabolisme. L'exposition à l'Al peut affecter les glandes mammaires se traduisant par des cancers et des kystes (Darbre, 2016). En plus de la source alimentaire, l'application cutanée des antitranspirants et autres produits cosmétiques à base d'Al peut représenter une source d'exposition locale à long terme. ...
... 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). Par ailleurs, une accumulation excessive de graisse et une augmentation du tissu adipeux provoquée par la toxicité de l'Al peuvent conduire à l'obésité (Mailloux et al., 2011). ...
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.
... Mice subjected to the same type of aluminum salt exposed to antiperspirants develop breast cancerous cells. Related effects were found in tests of human breast cell cultures [1][2][3]. It is also speculated that heavy metals have a role in sarcomas [4]. ...
... Nickel hydroxide is suitable for systems; which nickel amounts are unsafe. It was observed that CaNa [2] EDTA recovers brain damage from nickel chloride, and eliminates nickel from Cirrhinus mrigala [90]. ...
There has been a growing recognition regarding heavy metal toxicity owing to their position in cancer induction. The study is linked to heavy metals like titanium, arsenic, beryllium, cadmium, lead, mercury, nickel and radium. A meta-analysis was compiled using PubMed to determine existing exposure channels, forms of cancers caused, and treatment interventions for the metals. It was planned to lead potential study activities linked to heavy metals and cancer.
... Major routes of absorption are the skin, the nose, the lungs and the gastrointestinal system [7,8]. As a consequence of continuous exposure, aluminum accumulates in several organs including the lung, bone, liver, kidney, brain and mammary gland [7,9]. High levels of this metal have been associated with diseases such as osteomalacia, microcytic anemia, dialysis encephalopathy, Parkinson's, and Alzheimer's [10][11][12][13][14]. Aluminum has also been suggested to be a potential human carcinogen implicated in the etiology of breast cancer [15,16]. ...
... Two additional considerations, in our opinion, are important with regard to the concentrations of aluminum used in our experiments. The range we selected is based on the concentrations of aluminum measured in different human tissues where this metal accumulates [7,9], and they do not represent those measured in the blood stream of healthy patients (much lower) or aluminum-intoxicated patients, as Willhite et al. (2014) stated in their report [46]. This is an important point to appreciate the relevance of our data for human health. ...
Chromosome instability (CIN) consists of high rates of structural and numerical chromosome abnormalities and is a well-known hallmark of cancer. Aluminum is added to many industrial products of frequent use. Yet, it has no known physiological role and is a suspected human carcinogen. Here, we show that V79 cells, a well-established model for the evaluation of candidate chemical carcinogens in regulatory toxicology, when cultured in presence of aluminum—in the form of aluminum chloride (AlCl3) and at concentrations in the range of those measured in human tissues—incorporate the metal in a dose-dependent manner, predominantly accumulating it in the perinuclear region. Intracellular aluminum accumulation rapidly leads to a dose-dependent increase in DNA double strand breaks (DSB), in chromosome numerical abnormalities (aneuploidy) and to proliferation arrest in the G2/M phase of the cell cycle. During mitosis, V79 cells exposed to aluminum assemble abnormal multipolar mitotic spindles and appear to cluster supernumerary centrosomes, possibly explaining why they accumulate chromosome segregation errors and damage. We postulate that chronic aluminum absorption favors CIN in mammalian cells, thus promoting carcinogenesis.
... The current studies were carried out to review the literature relevant to the symptoms (Palesh et al., 2010) and risk factors (Angahar, 2017;Lakshmi et al., 2012) of breast cancer. The role of physical activity (Friedenreich, 2010), age (Bucholc et al., 2001), family history (Bakhshi et al., 2018;Lakshmi et al., 2012), race (Knaus, 2012), diet (Bandera et al., 2015) (Naseer et al., 2018;Naseer et al., 2019;Rehman et al., 2018;Tahir et al., 2018;Vainio et al., 2002), genetic factor (Antoniou and Easton, 2006;Martin and Weber, 2000), alcohol (Dumitrescu and Shields, 2005;Essex et al., 2014), smoking (Jee et al., 1999;Reynolds et al., 2004), obesity (Byrne et al., 1991;Schapira et al., 1990), estrogen Level (Byrne et al., 2013;Yarden et al., 2002), radiations (Land et al., 2003;Mattsson et al., 1993;Preston et al., 2002) and heavy metals (cadmium, chromium, arsenic, lead, nickel, aluminum and zinc) in breast cancer are also reviewed (Alatise andSchrauzer, 2010;Aquino et al., 2012;Cantor et al., 1995;Choe et al., 2003;Chunhabundit, 2016;Cui et al., 2007;Darbre, 2016;Farasani and Darbre, 2015;Florea and Büssel berg, 2011;Franklin and Costello, 2009;Gallagher et al., 2010;Health and Services, 1999;Johnson et al., 2003;Kilic et al., 2004;Liu et al., 2010;Mandriota et al., 2016;McElroy et al., 2006;Romaniuk et al., 2015;Ruiz-Ramos et al., 2009;Saleh et al., 2011;Schrauzer, 2008;Siewit et al., 2010;Sukumar et al., 1983;Sun et al., 2007;Ullah et al., 2019;Ying et al., 2009;Zhitkovich, 2011). developed nations have higher incidence rates (Angahar, 2017;Francies et al., 2020). ...
... Aluminum exposure is closely related to cause breast cancer. Mice were exposed to AlCl3resulting in malignant growth in mammary gland epithelial cells and the same effects were seen on the samples of human breast tissues (Darbre, 2016). Another research has also shown that exposure of Al to human breast cells has a tendency to produce uncontrolled growth (Mandriota et al., 2016). ...
Breast cancer is caused by uncontrolled growth of breast cells. It is more common in women as compared tothat in men. The breast cancer may be interlinked with the drinking of alcohol, smoking, sex, hormonal therapy, obesity,family history and age. Various epidemiologic studies suggest the role of metals e.g., nickel (Ni), zinc (Zn), arsenic(As),selenium (Se)and cadmium (Cd)as potential risk factors in breast cancer. Humans are exposed to these metals bymeans of drinking water, food and air. The oxidative theory suspects that the complexes formed from these metals invivo, near the location of DNA, catalyze the redox reactions which results in oxidation of DNA. The metals like arsenic(As), chromium (Cr), aluminum (Al), cadmium (Cd) and chromium (Cr)which exist in trace amount are considered ascarcinogens for organisms by IARC (International Agency for Research on Cancer). The carcinogenicity of these metalsmainly depends upon their chemical structure and oxidation states.
... Publications have highlighted the fact that excessive exposure to aluminium may cause genome instability in mammary gland epithelial cells, induce abnormal proliferation, and contribute to an increase in migration and invasion of cancer cells. In addition, aluminium (being a metalloestrogen) may produce an oestrogen-like effect, which is claimed to be implicated in the development of breast cancer [20]. However, the results of two epidemiological studies have failed to show a positive association between the use of antiperspirants and an increased risk of breast cancer [21,22]. ...
... W piśmiennictwie zwraca się uwagę, że nadmierna ekspozycja na glin może wywoływać niestabilność genomu w komórkach nabłonka gruczołów sutkowych, powodować nieprawidłową proliferację, jak również przyczyniać się do zwiększonej migracji i inwazji komórek nowotworowych. Ponadto glin jako metaloestrogen może mieć działanie podobne do estrogenów, którym przypisywany jest udział w powstawaniu nowotworów piersi [20]. Wyniki dwóch badań epidemiologicznych nie potwierdzają jednak pozytywnej korelacji między stosowaniem antyperspirantów a zwiększonym ryzykiem raka piersi [21,22]. ...
Excessive sweating (hyperhidrosis) is a common condition developing regardless of age, sex, and race, which often leads to a decrease in the quality of life. Depending on the cause, hyperhidrosis can be divided into the primary and secondary type (triggered by comorbidities, drugs, stress). Based on the degree of body involvement, hyperhidrosis may be either focal or generalised. Primary hyperhidrosis limited to certain body areas accounts for a vast majority of cases. According to the Canadian Hyperhidrosis Advisory Committee primary hyperhidrosis can be diagnosed if the symptoms persist for at least 6 months, and at least 4 of the following 6 criteria are fulfilled: bilaterally symmetric sweating, impairment of daily activities, more than 1 episode per week, age at onset < 25 years, positive family history, and absence of symptoms during sleep. First-line therapy of primary hyperhidrosis is based on topical medications. If no improvement is noted, systemic or surgical options are considered (e.g. iontophoresis, botulin toxin injections). In secondary hyperhidrosis, the focus is on the treatment of the underlying cause.
... This may be connected with the metastatic process of breast cancer (activating matrix metalloproteinase 9 (MMP9) and matrix metalloproteinase 14 (MMP14)). Lastly, Al is considered a proinflammatory and proapoptotic agent, up-regulating various cytokines such as Interleukin-1β and tumor necrosis factor α (TNFα) in numerous tissues [4,28,[54][55][56][57]. ...
Aluminium (Al) is the most ubiquitous metal in the Earth’s crust. Even though its toxicity is well-documented, the role of Al in the pathogenesis of several neurological diseases remains debatable. To establish the basic framework for future studies, we review literature reports on Al toxicokinetics and its role in Alzheimer’s disease (AD), autism spectrum disorder (ASD), alcohol use disorder (AUD), multiple sclerosis (MS), Parkinson’s disease (PD), and dialysis encephalopathy (DE) from 1976 to 2022. Despite poor absorption via mucosa, the biggest amount of Al comes with food, drinking water, and inhalation. Vaccines introduce negligible amounts of Al, while the data on skin absorption (which might be linked with carcinogenesis) is limited and requires further investigation. In the above-mentioned diseases, the literature shows excessive Al accumulation in the central nervous system (AD, AUD, MS, PD, DE) and epidemiological links between greater Al exposition and their increased prevalence (AD, PD, DE). Moreover, the literature suggests that Al has the potential as a marker of disease (AD, PD) and beneficial results of Al chelator use (such as cognitive improvement in AD, AUD, MS, and DE cases).
... However, excessive amounts of Al 3+ seriously threaten human health leading to several dangerous effects, particularly on the nervous system [5,6]. Indeed, the accumulation of Al 3+ in our organism causes numerous illnesses including Parkinson's and Alzheimer's disease and breast cancer [7][8][9][10][11][12]. Thus, the design and development of efficient methods for the satisfactory detection of Al 3+ ion seem to be an essential issue. ...
An efficient fluorescent cation chemosensor based on fluorescein L4 was well prepared and identified with spectroscopy analyses. UV–vis and fluorescence measurements examined the analyte complexation of the L4 with various cations, demonstrating a clear tendency to Al³⁺ ion. In the Job plot study, a stoichiometry ratio of a complex between L4 and Al³⁺ ion was determined to be 1: 2 (L4: Al³⁺). A stoichiometry ratio of complex between L4 and Al³⁺ ion was determined to be 1: 2 (L4: Al³⁺) using the Job plot. The association constant (Ka) of the L4-Al³⁺ complex was found 2.8 × 10⁷ M⁻². The obtained limit of detection (LOD) value (1.37 × 10⁻⁶ M for Al³⁺) exhibited the considerable sensitivity of the chemosensor L4 to Al³⁺ ion. DFT/TD-DFT calculations have also been employed to support the binding mode and photophysical properties of the complexation of chemosensor L4 to Al³⁺ ion and also to investigate the enhancement of L4 fluorescence by Al³⁺ ion.
... Coincidentally the upper outer quadrant of the breast is where there is also a disproportionately high incidence of breast cysts and breast cancer. Aluminium has been measured in human breast tissues/fluids at higher levels than in blood, and experimental evidence suggests that at physiologically relevant concentrations, aluminium can adversely impact human breast epithelial cell biology [108]. ...
Due to the rapid growth of the cosmetic industry in recent years, the development of new, reliable, cost-effective, ease of use and rapid methods to assay cosmetics’ quality is of particular importance. Modern electrochemistry provides powerful analytical techniques with excellent sensitivity, instrumental simplicity and portability, providing reliable alternatives to conventional analytical methods. This review aims to give readers a clear view of advances in areas of electrode modification, successful strategies for signal amplification, and miniaturization techniques used in electroanalytical devices for cosmetics control and safety. We have summarized recent trends in the nonenzymatic electrochemical sensor systems applied in the analysis of cosmetic products revealing that there are a variety of efficient sensors for whitening agents, preservatives, UV filters, heavy metals, etc. In conclusion, current challenges related to the sensors design and future perspectives are outlined.
... As contact is usually a result of polluted food and water ingestion, environmental contamination evidence sturdily support arsenic's function in developing lung and bladder cancer [7,8]. Aluminum exposed in the breast tissue was being positively linked with carcinogenesis [9,10]. Cadmium exposure was associated with cancer in several tissues including breast, stomach digestive tract, prostate, lungs and tests. ...
Background: Our life relies on our ability to use all sorts of materials, like trace elements, in the world for our needs. The using of heavy metals has greatly contributed to the comfort of our everyday lives. Blood is directly affected by poisoning when such metals are inhaled from environments where heavy metals occur in high levels. Research is constantly advancing our knowledge of the connection between various trace elements and disease, particularly cancer, since the effects of heavy metals on human health remain a serious health concern. Objective: The objective of this work is to establish levels of a range of elements in human blood, serum and hair samples of patient undergo lung cancer comparing with control (healthy persons) so that potential exposures can be better identified in future cases. Methods: Elements concentrations including As(arsenic), Ba(barium), Co(cobalt), Li(lithium), Mg(magnesium), Mn(manganese), Mo(molybdenum), Rb(rubidium), Sr(strontium) and Ti(titanium) was analysis used MS ICP (an inductively coupled plasma atomic absorption spectrophotometer). Results: Test found that Mn has substantially (p<0.05) high concentration in three tissues including whole blood, serum, and hair of patients with lung cancer (291,487.2,68.03) ug / l respectively. In comparison as occurs in the lowest concentration. Sr was 77.5ug / l, Rb 41.6ug / l, and Ba 35.2ug / g. On other hand, Co, Li, Mg, Mo and Ti were found in low levels ranged 1.7-5.5 ug/l, in whole blood of patients. Hair samples accumulated the lowest concentration of As, Ba, Co, Mg, Mn and Rb. When we compare the concentration of trace elements between lung patients and control samples, that clear most of the elements accumulate at high levels in lung cancer patients. Result found significantly high As, Ba, Co, Mg, Mo concentration in whole blood and serum of lung cancer patients, in contract, Li, Mn and Rb occur in high levels in whole blood of control sample. Even as hair of control samples have elevated levels of As, Sr and Ti. However, concentrations of trace elements in the whole blood of smokers and non-smokers showed that all ten elements accumulated at elevated levels in the blood of smokers relative to non-smokers. Spearman correlation found significantly positive correlation among trace elements in the blood of patients with smoker lung cancer and non-smokers. Conclusion: The study conclude that trace metals level in smokers persons are elevated than non-smokers. The findings of this study lend some support to the link between heavy metals pollution and lung cancer cases.
... 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.
... Aluminium-based salts are used as antiperspirant in underarm cosmetics and dermal absorption of aluminium from this use has been implicated in the development of breast cancer [36] . Aluminium has been measured in human breast tissue [37] and breast cyst fluid [38] at higher levels than in blood, and in nipple aspirate fluid at higher levels in samples taken from women with than without breast cancer [39] . ...
Estrogen disrupting chemicals are environmental compounds which mimic, antagonize or interfere in the action of physiological estrogens. They occur naturally (plant phytoestrogens) but the majority are man-made compounds, which, through their use in agricultural, industrial and consumer products, have become widely present in human tissues including breast tissue. Since exposure to estrogen is a risk factor for breast cancer, estrogen disrupting chemicals may also contribute to breast cancer development. This review discusses evidence implicating estrogen disrupting chemicals in increasing migratory and invasive activity of breast epithelial cells, in epithelial-to-mesenchymal transition, and in growth of breast tumours at metastatic sites as well as the primary site. Mechanisms may be through the ability of such chemicals to bind to estrogen receptors, but unlike for proliferation, effects on cell migration and invasion are not limited to estrogen receptor-mediated mechanisms. Furthermore, whilst effects on proliferation can be measured within hours/days of adding an estrogen disrupting chemical to estrogen-responsive breast cancer cells, effects on cell migration occur after longer times (weeks). Most studies have focused on individual chemicals, but there is now a need to consider the environmentally relevant effects of long-term, low-dose exposure to complex mixtures of estrogen disrupting chemicals on mechanisms of metastasis.
... Last but not least, a familiar BC and/or general predisposition to cancer may represent important risk factors (17,18), such as chronic fatigue, sleep disturbance and depression (20)(21)(22). Several studies have investigated the gene-environment interactions showing that BC risk is related to the common susceptibility variants, which can be altered by environmental factors, such as industrial air pollutants, soil or water contamination due to heavy metals and genotoxic agents, active or passive tobacco smoke (3,10,(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34). Finally, several occupational factors can expose workers to a higher risk of BC due to toxic compounds or exposure to ionising radiation, rotating night shifts or higher-status occupations (35)(36)(37)(38)(39)(40)(41)(42). ...
Breast cancer is the leading cause of cancer-associated amongst women worldwide. Several studies have shown that individual, environmental and occupational factors can serve an important role in the onset of breast cancer; although the majority of studies have demonstrated this association, and several studies have investigated the biological pathways, it is impossible to describe with certainty the causal relationship that involve circadian rhythm disruption and melatonin dysregulation with the oncogenic processes. Over the years, due to the introduction of more effective screening tools, an increase in the incidence of breast cancer as well as a decrease in the age at diagnosis has been witnessed. Subsequently, an increasing number of individuals have obtained care at a younger age, which has meant that after surgery and chemotherapy, these workers have had to return to work. In light of these paradigmatic changes, the aim of the present review was to identify potential targets for future organisational strategies that should be adopted in the workplace by occupational physicians, both for prevention and for the return-to-work process of working women who have suffered from breast cancer.
... L'alluminio, d'altra parte, viene anche eliminato mediante il latte, la bile, le feci, il sudore, i capelli, le unghie, il sebo e lo sperma [384][385] [355] . ~ 141 ~ Recenti studi sugli effetti tossici dell'alluminio hanno riportato tossicità a livello dell'apparato riproduttivo [340] , lesioni polmonari [341] [342] , coinvolgimento a livello del seno [343] , anomalie ossee [344] [345] , tossicità a livello immunitario [346] e disturbi neurologici [347] [348] . ...
during the covid lockdown there was an increased consumption of both natural and synthetic supplements. the aim of this thesis is to analyze the heavy metal amount in spices and plants used to create the supplements
... It is well-known that some metals such as magnesium, iron and zinc are necessary for body activities and they must intake via nutrition, while aluminum is unnecessary for body (Stahl et al. 2017). People can intake aluminum from two main sources; through food and dermal contact (Al-based antiperspirant salts are widely used to reduce perspiration in the armpit area) , Dabre 2016, Stahl et al. 2011. When considered Table 1, it is possible to classify these sources as "external sources" and "dietary sources". ...
Several studies have shown the relationship between the aluminum exposure and the Alzheimer's disease. The gastrointestinal absorption of Aluminum (Al) is low. Also, If the renal filtering system works as needed, generally urine can be enough to eliminate overdose (rational over concentrations) of Al. But Al can be found in kinds of foods and drinks such as processed foods (because of additives, packaging materials, utensils…), fresh vegetables and fruits (because of soil) and even in drinking water therefore, in some cases, the Al level may pose a health risk. Chronic high concentration to Al exposure preferably intakes by oral, intravascular ways with also not having a good condition of Glomerular Filtering System of Kidneys (GFR). Nowadays, although mankind is having more Al by oral ways than past and many studies have been conducted to determine whether there is a relationship between aluminum and Alzheimer’s disease(AD) or not. Therefore, this review is intended to provide a short summary of the works done in the past and it may warn people about Al intake in the next decade, therefore human can change their life to be more natural less industrial.
... Aluminum (Al) has toxic effects on several body organs such as brain and kidneys and also on bones and blood. It is well known that aluminum plays a role in some neurodegenerative diseases, disturbs various enzymes and biomolecules and causes Alzheimer's disease [63]. ...
Water is a fundamental requirement for all living beings and it is considered as the most diverse solvent. It has a unique polarity and a distinctive set of properties due to hydrogen bonding. Water, being a universal solvent, can easily be polluted by absorption, adsorption and suspension of a lot of materials into it. Major sources of water contamination include the disposal of untreated garbage, milling, industrialization, and urbanization. Water is easily polluted by substantial metals including Lead (Pb), Arsenic (As), Copper (Cu), and Chromium (Cr). Water contamination can lead to serious illnesses and sometimes it is so hazardous that it can cause the death of a living organism.
... Al accumulation occurs most commonly via high-Al dialysate, ingestion, occupational exposure, cosmetics, medication, and adjuvant exposure (Bojórquez-Quintal et al. 2017;Boran et al. 2013;Chen et al. 2010). Recent reviews described the correlation between Al exposure and reproductive toxicity, pulmonary lesions, breast cancer, bone abnormalities, immunotoxicity, nephrotoxicity, hepatotoxicity, cardiotoxicity, hematological changes that induced anemia, and neurological disorders such as dialysis encephalopathy, Parkinsonism dementia, and Alzheimer's disease in heavily polluted sites (Colomina and Peris-Sampedro 2017;Daniel et al. 2007;Darbre 2016;Elizabeth et al. 2020;Ellman et al. 1961;Exley 2014;Exley and House 2011;Fulgenzi et al. 2014;García-Pérez 2012;Garrosa et al. 2011;Ghorbel et al. 2017) . The chain of Al intake, absorption, and elimination is variable. ...
This study aimed to evaluate the effect of daily sublethal doses of aluminum (Al) on hematological, physiological, biochemical, and behavioral changes in male albino Wistar rats. In addition, Al tissue accumulation and histopathological changes in the cerebral cortex, liver, and kidney were examined. The rats were randomly separated into three groups. Group 1 included rats who received the median deadly dose (LD50) of aluminum chloride (AlCl3), group 2 served as the control, and group 3 was treated with a non-lethal dose of AlCl3 (1.5 mg/kg) intraperitoneally for 45 days. At defined time intervals, hepatic and renal specific enzymes and biochemical activity were measured. In addition, we examined Al accumulation, the condition of the liver via histological methods, and the impact on the cerebral cortex. In comparison to the controls, rats treated with AlCl3 exhibited a rise in AST, ALT, and ALP enzyme activity. We also saw a significant decrease in body weight and a decrease in total protein, lipids, cholesterol, acetylcholinesterase (AChE), RBCs, and Hb levels compared to the control group. Histopathological examination suggested severe changes in the liver, kidney, and cerebral cortex of the rats. The current study indicates that sublethal daily exposure to AlCl3 causes hazardous effects, as increased Al concentration in the body is shown to induce detrimental biochemical and histological changes as well as decreased body weight. Therefore, careful attention should be given to treatments requiring long exposure in patients and the potential for accumulation via food and drinking.
... Accumulating evidence has demonstrated that high levels of aluminum are related to breast cancer and other pathological conditions, such as dialysis dementia, osteomalacia and neurodegenerative diseases (35). Combined with these studies, the potential association of Al and LUSC provides clues for subsequent mechanisms research and epidemiological studies. ...
Background
Lung cancer is the most common cancer and the leading cause of cancer-related mortality worldwide. Environmental chemicals play a significant role in tumorigenesis, it is necessary to explore the lung cancer-related chemicals and provide new clues for neoplastic prevention and treatment.
Methods
The genome-wide association study (GWAS) summary data of malignant neoplasm of bronchus and lung (C34) were downloaded from the UK Biobank. It includes 1,655 samples and 450,609 controls. DNA methylation profiles of non-small cell lung cancer were obtained from the GEO database (GSE75008). A transcriptome-wide association study was applied to detect genes significantly related to lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) by FUSION software. Comparative toxicogenomics database (CTD) enables the construction of chemical-gene-disease networks. We conducted a chemical-related gene set enrichment analysis (GSEA) based on GWAS summary data, DNA methylation data, and the CTD to explore the relationships between chemicals and two major histological subtypes of lung cancer. Venn analysis was used to identify the common related chemicals of the GWAS summary data and the DNA methylation data.
Results
We detected aluminum, naringenin, and 2-acetylaminofluorene as LUSC-related chemicals and antirheumatic agents, nickel monoxide, and 2-amino-2-methyl-1-propanol as LUAD-related chemicals.
Conclusion
By integrating GWAS and chemical-gene interaction networks, we made linkages between various chemicals and lung cancer on genetic basis. Moreover, this study provided new clues for exploring the etiology of lung cancer and a new method for finding the chemicals related to tumor or other complex disease.
... Several studies reported that Al was one of the contributors to breast cancer [4,5]. On the other hand, lead (Pb) is particularly dangerous to children. ...
Using biodegradable polymer polycaprolactone (PCL) and zeolite, the present experiment was conducted with the aim of using biodegradable PCL and zeolite based composite membrane to remove silver in drinking water. After optimizing the electrospinning parameters, a double-layered PCL and PCL/zeolite electrospun composite membranes were manufactured. The membranes were then characterized using a scanning electron microscope (SEM) and an energy dispersive X-ray (EDX) and the filtration phenomenon was conducted by dispersing silver nanoparticles in water. After comparing the filtration results using an inductively coupled plasma optical emission spectrometry (ICP-OES), it was observed that the bi-layered membrane filtered 90% of silver present in the water. The present work shows that the new PCL/zeolite based double-layered membrane can be promising to remove contaminants in drinking water.
... In recent years, it has been reported that aluminum may be involved in the occurrence of tumors. A few studies found that the content of aluminum was higher in tumor tissue than in control tissue in breast cancer and colorectal cancer [43,44], while others reported opposite result in laryngeal cancer [45], suggesting a different distribution of aluminum in different tumor tissues. It has been reported that cisplatin treatment significantly affected aluminum metabolism and upregulated plasma aluminum level in rabbits, but there was no difference in liver and kidney tissues [46]. ...
Background and aim:
Major and trace elements play an important role in human body, and it has been reported that ionomic distribution differ greatly in tumor patients. The aim of the present study was to investigate the effects of cisplatin-based neoadjuvant chemoradiotherapy on the ionomic profile in human plasma as a potential biomarker for the therapeutic effects of cervical cancer.
Method:
Thirty-seven patients with cervical cancer receiving neoadjuvant chemoradiotherapy were included in this study, pretherapy and post-treatment blood samples were collected and concentrations of 24 ions were analyzed by inductively coupled plasma mass spectrometry (ICP-MS).
Results:
The results showed that after cisplatin chemotherapy and radiotherapy, patients' plasma Pt level significantly increased, Na, Mg, P, K, Ca, Se, Cu, Zn, Se, Sr, Ba levels significantly decreased (P < 0.01), and Al, Cu ions were significantly correlated with the treatment effect (P < 0.05). In addition, the pattern of elemental correlations changed dramatically after the neoadjuvant chemoradiotherapy.
Conclusion:
The results indicated that the plasma ionomic profile may serve as a quick and convenient tool to reflect the therapeutic effect of cisplatin-based chemoradiotherapy in cervical cancer patients, and supplement of certain essential elements may be of great importance for the maintenance of ion homeostasis in human body and for the reduction of adverse effect of chemotherapy and radiotherapy.
... The human population is exposed to aluminium (Al) from diet, antacids and vaccine adjuvants, but frequent application of Al-based salts to the underarm as antiperspirant adds a high additional exposure directly to the local area of the human breast (Exley, 2013). Al has been measured in human breast tissues/fluids at higher levels than in blood, Al can adversely impact on human breast epithelial cell biology (Darbre, 2016). Aluminium's free metal cation, Alaq3+, is highly biologically reactive. ...
An accurate simple, rapid and direct spectrophotometric method for the determination of aluminium in presence of iron (III) was developed. The method is based on the reaction of aluminium (III) with xylenol orange at pH 4.3 using potassium hydrogen phthalate buffer solution to form a stable orange-red coloured complex which has maximum absorption at 512 nm. This study is showing the effect of triton X-100 on the spectrophotometric determination of aluminium which effected the stability, limits of Beer's law, blanck value and final absorption spectrum. Beer's law was obeyed over the range of (1-200) µg/25 ml (i.e 0.04-8.0 ppm). The molar absorptivity and Sandell's sensitivity of the coloured complex are 1.173×10 4 l.mol-1 .cm-1 , 0.00230 µg.cm-2 respectively. The interference caused by iron (III) was suppressed by adding sodium cyanide as masking agent. The method has been applied successfully for determining aluminium (III) in various water samples. The same work was done for the spectrophotometric determination of aluminium in the absences of triton X-100. While the analytical parameters recorded are 1.045×10 4 l.mol-1 .cm-1 , 0.00258 µg.cm-2 , the molar absorptivity and Sandell's sensitivity of the coloured complex respectively, and limits of Beer's law are (5-100) µg/25ml (i.e. 0.2-4.0 ppm).
Several pollutants can alter neonatal prostatic development predisposing this gland to diseases. The toxicity and endocrine disrupting potential of aluminum has been reported in many organs, but little is known about its effects on the prostate. This study aimed to evaluate the effects that aluminum neonatal exposure can cause in the male ventral prostate and in the female prostate of adult and senile gerbils. Male and female pups were treated orally with aluminum chloride (10 mg/kg) from the 1st to the 14th day life. After treatment, the animals were aged until they reached 90 days or 1 year of life. The prostate glands were dissected out and submitted to morphological, immunohistochemical and ultrastructural analyses. Ventral prostates of adult males showed moderate hyperplasia and increased epithelial proliferation not associated with androgen receptor (AR) deregulation. On the other hand, senile males showed intense prostatic hyperplasia, and increased cell proliferation and epithelial AR regulation. Additionally, at both ages, there was a reduction in the prostate secretory function. The morphological changes observed in the female prostate were like those found in males. However, in adult females, prostatic hyperplasia was accompanied by a lower regulation of AR and estrogen receptor alpha, while in senile females, intense hyperplastic growth was associated with an increase in estrogen receptor alpha and a reduction in stromal AR. These results demonstrate that aluminum chloride neonatal exposure alters the hormonal regulation of the male and female prostate, inducing tissue damage that occurs in adulthood and intensifies during aging.
Endocrine-disrupting compounds (EDC) play an important role in the increased incidence of breast cancer (BC). There are some 160 xenoestrogens that may be involved in the development of BC. Much less is known about the influence of xenoestrogens on the effectiveness of the treatment of BC. The aim of this study was to analyze the interaction of metalloestrogens (aluminum and chromium (III)) and drugs used in the treatment of hormone-dependent BC—aromatase inhibitors (AI)—letrozole and exemestane. A cell viability assay, a flow cytometer analysis of apoptosis and cell cycle phases, and protein activity of BAX and Bcl-2 were performed on two human breast cancer cell lines—MCF-7 and MCF-7/DOX. In MCF-7 cells, the lower concentration of exemestane and higher of letrozole, in combination with metalloestrogens, results in a decrease in the effectiveness of drugs. Additionally, in the MCF-7/DOX cell line, we observed that the combination of metalloestrogens and AI leads to a decrease in the drug’s effectiveness due to an increase in the viability of breast cancer cells (both concentrations of letrozole and higher concentration of exemestane). In both cell lines, the reduction in the effectiveness of AI, in combination with metalloestrogens, is not related to the influence on the cell cycle. Our results confirm that exposure to metalloestrogens may negatively affect the effectiveness of hormone therapy with AI. Further studies are needed to fully explain the mechanism of these interactions.
Connu être un métal omniprésent dans la nature, l'homme est exposé à l'aluminium (Al) selon différentes sources induisant à des maladies émergentes. L’apport alimentaire joue un rôle majeur dans son accumulation organique. La prévalence élevée des maladies associatives avec le métal au Liban a été le point de départ de cette étude, afin d'explorer l'exposition alimentaire révélant toute association entre la consommation alimentaire, les maladies et les niveaux plasmatiques d'Al. Cette étude vise à estimer les taux de consommation alimentaire à base d'Al et à quantifier les taux d'Al dans différentes matrices alimentaires, révélant les principaux contributeurs de l'exposition à l'Al pour la population libanaise. Deux études transversales ont été menées à l'aide d'un questionnaire électronique personnalisé sur la fréquence alimentaire. La première étude ciblait des personnes âgées de 18 à 64 ans de différentes régions libanaises, réparties proportionnellement dans le but d'étudier la consommation alimentaire à base d'Al. La sélection des aliments était basée sur les résultats de l'étude française EAT2. La deuxième étude ciblait 100 participants, y compris des femmes enceintes, visant à corréler la consommation alimentaire avec les niveaux plasmatiques (e-FFQ) et à révéler toute association de maladie. Les niveaux d'Al ont été analysés par spectrométrie d'absorption atomique. L'analyse des données a été réalisée par le logiciel SPSS version 25.Le questionnaire a été complété par 167 participants. En outre, 97 aliments ont été étudiés en 2018. Les niveaux d'Al avaient une moyenne de 3,56 ± 2,08 mg / kg (allant de 0,14 à 9,37). Les niveaux d'Al les plus élevés ont été trouvés dans les légumes, suivis des sauces et condiments, des bonbons et des plats cuisinés. L'apport hebdomadaire tolérable provisoire (AHTP) d'Al a été fixé à 0,50 mg / kg du poids corporel (60 kg / personne). La deuxième étude a révélé une exposition positive aux aliments avec une corrélation de 32 % avec les niveaux plasmatiques moyens d'Al (atteignant 2,16 ± 1,30 μg / L); spécifiquement avec les légumes, les fruits, les pommes de terre, les légumineuses, le pain, la pâtisserie, les boissons gazeuses et les plats cuisinés. L'âge, l'état de grossesse et l'utilisation d'ustensiles de cuisine en Al étaient associés à des niveaux plasmatiques d'Al plus élevés, contrairement à la carence en vitamine D, à l'anémie, à l'arthrite et aux ulcères. La population libanaise, avec l'inclusion des femmes enceintes, est exposée à Al par l'ingestion d'aliments à base d'Al dans la limite des seuils internationalement établis d'apport tolérable (1 mg / kg / semaine), bien qu'elle reste protégée de certaines maladies liées au métal. Une recommandation nationale devrait être établie afin de maintenir des niveaux inférieurs de contamination des aliments par Al, limitant ainsi son augmentation dans l'organisme. Des recherches supplémentaires devraient être entreprises pour explorer la contamination par l'Al en tant que triade dans les aliments, l'eau et le sol.
Aluminum (Al) is a widespread metal in the environment, and is found in fresh or processed foods, household utensils, packaging, and medicines. In addition to its high toxicity, Al can also have estrogenic agonistic effects on target organs. Considering that the Al effects on the prostate are little known, the aim of this study was to evaluate the impact of aluminum chloride (AlCl3) subacute exposure on the morphophysiology of the male ventral prostate and the female prostate of adult gerbils. Furthermore, the glandular restoration capacity in face of the Al insults was evaluated in gerbils that were submitted to 30 days of recovery. Male and female gerbils were orally exposed to AlCl3 (10 mg/kg) for 30 consecutive days. The animals were euthanized 1 day (Al1D) or 30 days (Al30D) after the end of treatment. Prostates were dissected out and processed for structural, ultrastructural and immunohistochemical analyses. Male ventral prostates and female prostates of the Al1D group showed increased cell proliferation, glandular hyperplasia, increased secretory activity and greater androgen receptor immunoreactivity. In males, Al withdrawal (Al30D) allowed a partial recovery of the prostate, as the glandular secretory activity, and frequency of androgen receptor positive cells were similar to the control group. In females, the recuperation interval (Al30D) was not enough to restore the prostatic morphology, since the gland remained hyperplastic, proliferative, and with greater androgen and estrogen receptor immunoreactivity. These data alert to the importance of avoiding Al exposure, since this metal can have a harmful and prolonged action on the prostate.
Endocrine-disrupting chemicals (EDCs) occur in air as volatile or semivolatile compounds in the gas phase or attached to particulate matter. They include industrial chemicals (polychlorinated biphenyls), products of combustion (polychlorinated dibenzodioxins/furans, polycyclic aromatic hydrocarbons), pesticides, herbicides alkyl phenols, components of plastics (phthalates, bisphenol A), components of consumer goods (parabens, triclosan, organobromine flame retardants, fluorosurfactants, fragrance compounds), and some metals. This chapter discusses the sources of EDCs in air, measurements of levels of EDCs in outdoor and indoor air, and the contribution of EDCs in air to overall human body burdens and to human endocrine health.
This chapter provides an introduction to the importance of hormones to the healthy functioning of the human body and an overview of the varied types and sources of environmental chemicals that can interfere in their action. Such compounds, termed endocrine-disrupting chemicals (EDCs), may occur naturally, but the majority are man-made compounds that have been released into the environment without prior knowledge of their impact on animal welfare or human health. The chapter begins with some historical background, especially related to the endocrine-disrupting effects of EDCs in wildlife, and then outlines general mechanisms by which EDCs may disrupt hormone activity. Descriptions are then given of the range of compounds that are EDCs, their chemical structures, and the sources of exposure for the human population.
Many hundreds of endocrine disrupting chemicals (EDCs) have been measured as entering human breast tissue from a range of environmental sources, and this review focuses on discussion of mechanisms by which such EDCs may be contributing to the globally rising incidence of breast cancer. Many of the distinguishing features of breast cancer may be accounted for by EDC exposure, including, but not limited to, the fact that many EDCs possess estrogenic activity and exposure to estrogen is a main risk factor for breast cancer. Studies of the actions of EDCs in human breast cancer cells are aided by use of the conceptual framework of the hallmarks of cancer, and, acting by a variety of genomic and nongenomic mechanisms, EDCs have now been shown to enable all the hallmarks of cancer to develop in human breast cancer cells. Many studies report that hallmarks can develop at concentrations which are within the range of those measured in human breast tissues, especially when added as mixtures. The varied levels of different EDCs measured in individual breast tissue samples together with the overlapping and complementary mechanisms of action of the EDCs imply that thematic mechanisms will be driven inevitably by different chemical mixtures. Despite the complexity, EDCs do need to now be acknowledged as a risk factor for breast cancer in order for preventative strategies to include reduction in EDC exposure.
The aim of the study was to investigate the possibility of using а concentration of aluminum as a marker of neurodegenerative diseases.
Material and methods . To achieve this goal, there was carried out an analysis of literary origins from various databases, in particular Scopus and PubMed.
Results . The analysis shows that by now there has been accumulated strong evidence that certain neurodegenerative diseases are associated with chronic exposure to low-dose of aluminum: in particular, Alzheimer's disease (AD); motor neuron disease or amyotrophic lateral sclerosis (ALS); multiple sclerosis (MS) and a number of others.
Conclusion . Thus, it can be assumed that the measurement of the concentration of Al in the blood plasma will make it possible to identify a group people with of high risk of AD, which will allow starting preventive treatment at the earliest stage of the disease. The capabilities of the existing methods of analysis: atomic absorption spectrometry with electrothermal atomization (GFAAS) and inductively coupled plasma mass spectrometry (ICP-MS) enable to solve this problem.
Excessive sweating and body odors in many cultures can cause negative perceptions of an individual and in many cases is related to poor hygiene. Personal hygiene products have been developed with the intention of preventing these undesirable issues. The aim of this paper is to review the main active ingredients used in marketed deodorant and antiperspirant formulations as well as to identify new strategies and future methods to optimize such products and prevent malodor. PubMed and ScienceDirect databases were used to search for studies reporting the use of deodorants and antiperspirants, the compounds used in the formulations, their mechanisms of action and associated controversies, as well as new trends and approaches in the area. Even today, we are still using well-known and established actives such as triclosan and aluminum salts, and these are still the most used compounds in deodorants with bactericidal and antiperspirant properties. These substances have been on the market for more than 40 years, and still there are many questions concerning the safety of both actives. There is a general increased interest globally for lifestyles that focus on sustainability and more natural products such as plant sources and the use of, for example, essential oils. The research that focuses in the area of antiperspirants and deodorants is now more focused on studies of the armpit biochemistry and function and control of the microbiota present in this area. Other possible areas of interest are biotechnological solutions and finding new compounds that will interfere with the biochemistry of the process of sweat decomposition. Further approaches include formulations with probiotics which would maintain the balance of axillary microbiota.
Background
Effective topical treatment options for patients with primary axillary hyperhidrosis are limited. Recent phase 1 trial showed promising results regarding efficacy and safety for topical cream containing glycopyrronium bromide (GPB).
Objective
To assess efficacy, safety and tolerability of a 4‐week topical treatment with 1% GPB cream in subjects with primary axillary hyperhidrosis compared to placebo.
Methods
171 patients (84 placebo; 87 1% GPB) with primary axillary hyperhidrosis were included in this 4 week, multicenter, randomised, double‐blind, placebo‐controlled Phase 3a part of the pivotal study. Sweat production was measured by gravimetry. Patients rated disease impact using the Hyperhidrosis Disease Severity Scale (HDSS) and Hyperhidrosis Quality of Life Index (HidroQoL©).
Results
Absolute change in sweat production from baseline to day 29 in logarithmic values was significantly larger in the 1% GPB group than in the placebo group (p=0.0038). The improvement in HidroQoL© exceeded minimal clinically important difference of 4. The proportion of responders was two‐fold higher than for placebo for sweat reduction, HDSS and HidroQoL© (‐197.08 mg GPB vs. ‐83.49 mg placebo; 23% GPB vs 11.9% placebo and 59.8% GPB vs. 26.2% placebo respectively). Treatment was safe, most TEAEs were mild or moderate and transient. Local tolerability was very good with 9.2% of patients having only mild or moderate application site reactions. The most reported ADR was dry mouth (16.1%), an expected anticholinergic effect of the treatment.
Conclusion
1% GPB cream may provide an effective new treatment option exhibiting a good safety profile for patients with primary axillary hyperhidrosis. The long‐term open‐label part (Phase 3b) is ongoing.
Several studies highlight the presence of aluminum and diclofenac in water bodies around the world and their ability to induce oxidative stress and a negative effect on biomolecules in several aquatic species. However, studies evaluating the toxic effect of mixtures of these contaminants are scarce. The objective of this work was to determine the genotoxic, cytotoxic and embryotoxic effect of the mixture of aluminum and diclofenac at environmentally relevant concentrations on Cyprinus carpio.
Juveniles of Cyprinus carpio were exposed to 0.31 μg L⁻¹ of diclofenac, 24.45 mg L⁻¹ of aluminum, and a mixture of both contaminants at the same concentrations for 12, 24, 48, 72 and 96 h. After the exposure time the liver, gills and blood were extracted and the following biomarkers were evaluated: micronucleus frequency, comet assay, caspase activity and TUNEL test. On the other hand, Cyprinus carpio embryos were exposed to diclofenac (0.31 μg L⁻¹), aluminum (0.06 mg L⁻¹) and their mixture at the same concentrations and exposure time. Microscopic observation was performed to evaluate embryonic development at 12, 24, 48, 72 and 96 h.
Diclofenac (0.31 μg L⁻¹) induces significant increases in micronucleus frequency with respect to control (p < 0.05), in all tissues. Aluminum (24.45 mg L⁻¹) significantly increases DNA damage index in liver and blood cells with respect to control (p < 0.05). All treatments increase caspases activity in all tissues with respect to control (p < 0.05). Diclofenac increases the percentage of TUNEL-positive cells in liver and blood; while aluminum and the mixture increases it significantly in gills and blood with respect to the control (p < 0.05). The mixture significantly delays embryonic development, while aluminum and the mixture significantly increase teratogenic index with respect to control (p < 0.05). In conclusion, exposure to environmental concentrations of aluminium, diclofenac and their mixture induces genotoxic damage, cell death by apoptosis and negative effects on the development of Cyprinus carpio and the toxic response is modified by the interaction of the xenobiotics.
Résumé
L’hyperhidrose ou hypersudation est définie comme une sudation incontrôlable, excessive et non prédictible qui dépasse les besoins liés à la thermorégulation. Elle touche préférentiellement les creux axillaires, les paumes des mains, les plantes des pieds et la face, mais peut affecter n’importe quelle partie du corps. Ce symptôme, en apparence bénin, peut avoir un retentissement négatif majeur sur la qualité de vie allant parfois jusqu’à l’isolement et la dépression. Par ailleurs, dans certains cas l’hyperhidrose peut être secondaire à une pathologie sous-jacente, parfois maligne, qu’il faut savoir identifier rapidement. En conséquence, chaque médecin devrait être capable d’élaborer une démarche diagnostique et thérapeutique devant ce motif de consultation relativement fréquent et probablement sous-diagnostiqué et sous-traité. Dans cet article, nous proposons une mise au point sur l’hyperhidrose de son diagnostic à sa prise en charge.
: Cutaneous exposure to aluminum may occur via contact with metal items, medications, and personal care products. Despite the widespread use of aluminum, allergic contact dermatitis is relatively rare. Sensitization is often incidentally identified during patch testing with aluminum-based chambers. This article presents several cases along with a literature review summarizing prevalence and clinical manifestations of cutaneous reactions to aluminum, recommendations for patch testing, sources of aluminum, and reproducibility of aluminum allergy over time.
Backgroung
Exposure to environmental pollutants in critical developmental windows may predispose the prostate to permanent changes in its homeostasis. Thus, it is essential to know the effects that environmental toxics, such as aluminum, can cause during the development of this gland. The aim of this study was to evaluate the effects of neonatal aluminum exposure on the ventral male prostate and the female prostate of 15 days old gerbils.
Methods
Male and female gerbils were exposed orally to 10 mg/kg/day of aluminum chloride from the 1st to the 14th postnatal day life. At 15 days of life, gerbils were euthanized and their prostates were collected for biometric, morphological, morphometric, immunohistochemical and three-dimensional reconstruction analyzes.
Results
Al exposure caused a reduction in body weight in males and a significant increase in serum testosterone levels in females. Prostate branching morphogenesis was intensified in males, who had greater length, number and area of prostatic epithelial buds. Additionally, Al altered the prostate hormonal regulation of males and females, causing up regulation of the androgen receptor and estrogen receptor alpha in the female prostate, and increased immunostaining of the androgen receptor in the ventral male prostate. These changes were associated with an increased rate of epithelial and stromal cell proliferation in both sexes.
Conclusion
Together, these results indicate that Al altered the neonatal development of the prostate and that this metal acted as an endocrine disruptor in this gland.
Résumé
Les termes déodorants et antitranspirants sont très souvent confondus alors que les mécanismes d’action des uns et des autres ainsi que les substances actives employées sont totalement différents. Il est certain que les antitranspirants sont obligatoirement déodorants par manque de substrat à décomposer. Ils représentent cependant un groupe de produits bien particulier qui génère des problèmes spécifiques par suite de la présence d’aluminium chlorhydrate ou ACH (Al2(OH)5Cl, 2 H2O), d’aluminium sesquichlorhydrate ou de complexe d’aluminium-zirconium entraînant après hydrolyse une acidification intense de la peau, d’où l’importance des émollients et des régulateurs de pH dans les formulations. Par ailleurs, l’aluminium par voie systémique est soupçonné d’être génotoxique et de promouvoir l’apparition de cancers du sein, engendrant ainsi de nombreuses controverses scientifiques. Or, son éventuelle toxicité par voie topique est liée à sa capacité de pénétration cutanée encore mal connue mais estimée très faible, ce qui peut rassurer sur son utilisation dans les produits cosmétiques. Son implication dans la maladie d’Alzheimer n’a pas été prouvée. En revanche, les sels de zirconium sont considérés comme toxiques et partiellement réglementés en Europe. Les problèmes posés par les déodorants sont ceux de la présence d’antiseptiques (triclosan, acide usnique) pouvant induire des résistances bactériennes mais plus sûrement la présence de dermatites axillaires dues au potentiel allergène des constituants de parfums et des huiles essentielles (isoeugénol, citronellal, lyral, aldéhyde cinnamique, etc.).
In 2017, the German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the biological tolerance value (BAT value) for aluminium [7429‐90‐5]. Available publications are described in detail. The BAT value of 60 µg aluminium/g creatinine evaluated in 2009 was based on the linear correlation between external and internal exposure. The aim of this re‐evaluation was the derivation of a health‐based BAT value considering the most sensitive critical effect of aluminium, the neurotoxicity. For this purpose, the available studies of aluminium‐exposed workers were taken into account, when the internal aluminium exposure as well as the occurrence of subclinical neurotoxic effects were determined. The effects had been measured with standardised neuropsychological test procedures. From these studies, a no observed adverse effect level (NOAEL) of 50 µg/g creatinine for the occurrence of subtle neurotoxic effects of humans was estimated. Therefore, a BAT value of 50 µg aluminium/g creatinine was evaluated. Sampling time for long‐term exposures is at the end of the shift after several shifts.
The detection, differentiation, and especially visual quantification of target compounds have always been one of the most important and interesting challenges for leading researchers. The quantitative diagnosis of contaminants by the naked eye is the easiest and most practical method to identify pollutants. Here we present a new and innovative way to detect and estimate the amount of aluminum ion in aqueous and non-aqueous solutions by a unique sacrificial Metal-Organic Framework. This unique MOF (TMU-60: [Zn(OBA)(L*)].DMF which the L* is 5,6-dipyridin-4-yl-1,2,3,4-tetrahydropyrazine), due to its special interaction with the aluminum ion, even in negligible ppb values (>500 ppb), leads to a quantitative degradation and subsequently solvent color change from colorless to red that can easily be detected by the naked eye. Also, the exact determination of the amount and even the detection of its lower values are possible by turn-on fluorescence property of TMU-60 (The detection limit (LOD) is 100 ppb).
Use of underarm aluminium (Al)-based antiperspirant salts may be a contributory factor in breast cancer development. At the 10th Keele meeting, Al was reported to cause anchorage-independent growth and double strand DNA breaks in MCF10A immortalised non-transformed human breast epithelial cells. We now report that exposure of MCF10A cells to Al chloride or Al chlorohydrate also compromised DNA repair systems. Long-term (19-21weeks) exposure to Al chloride or Al chlorohydrate at a 10(-4)M concentration resulted in reduced levels of BRCA1 mRNA as determined by real-time RT-PCR and BRCA1 protein as determined by Western immunoblotting. Reduced levels of mRNA for other DNA repair genes (BRCA2, CHK1, CHK2, Rad51, ATR) were also observed using real-time RT-PCR. Loss of BRCA1 or BRCA2 gene function has long been associated with inherited susceptibility to breast cancer but these results suggest that exposure to aluminium-based antiperspirant salts may also reduce levels of these key components of DNA repair in breast epithelial cells. If Al can not only damage DNA but also compromise DNA repair systems, then there is the potential for Al to impact on breast carcinogenesis.
Copyright © 2015 Elsevier Inc. All rights reserved.
The extracellular matrix (ECM) is the complex network of proteins that surrounds cells in multicellular organisms. Due to its diverse nature and composition, the ECM has a multifaceted role in both normal tissue homeostasis and pathophysiology. It provides structural support, segregates tissues from one another, and regulates intercellular communication. Furthermore, the ECM sequesters a wide range of growth factors and cytokines that may be released upon specific and well-coordinated cues. Regulation of the ECM is performed by the extracellular proteases, which are tasked with cleaving and remodeling this intricate and diverse protein matrix. Accordingly, extracellular proteases are differentially expressed in various tissue types and in many diseases such as cancer. In fact, metastatic dissemination of tumor cells requires degradation of extracellular matrices by several families of proteases, including metalloproteinases and serine proteases, among others. Extracellular proteases are emerging as strong candidate cancer biomarkers for aiding and predicting patient outcome. Not surprisingly, inhibition of these protumorigenic enzymes in animal models of metastasis has shown impressive therapeutic effects. As such, many of these proteolytic inhibitors are currently in various phases of clinical investigation. In addition to direct approaches, aberrant expression of extracellular proteases in disease states may also facilitate the selective delivery of other therapeutic or imaging agents. Herein, we outline extracellular proteases that are either bona fide or probable prognostic markers in breast cancer. Furthermore, using existing patient data and multiple robust statistical analyses, we highlight several extracellular proteases and associated inhibitors (eg, uPA, ADAMs, MMPs, TIMPs, RECK) that hold the greatest potential as clinical biomarkers. With the recent advances in high-throughput technology and targeted therapies, the incorporation of extracellular protease status in breast cancer patient management may have a profound effect on improving outcomes in this deadly disease.
Breast cancer is the most common malignancy among females. 5%-10% of breast cancer cases are hereditary and are caused by pathogenic mutations in the considered reference BRCA1 and BRCA2 genes. As sequencing technologies evolve, more susceptible genes have been discovered and BRCA1 and BRCA2 predisposition seems to be only a part of the story. These new findings include rare germline mutations in other high penetrant genes, the most important of which include TP53 mutations in Li-Fraumeni syndrome, STK11 mutations in Peutz-Jeghers syndrome, and PTEN mutations in Cowden syndrome. Furthermore, more frequent, but less penetrant, mutations have been identified in families with breast cancer clustering, in moderate or low penetrant genes, such as CHEK2, ATM, PALB2, and BRIP1. This paper will summarize all current data on new findings in breast cancer susceptibility genes.
The proteins encoded by the two major breast cancer susceptibility genes, BRCA1 and BRCA2, work in a common pathway of genome protection. However, the two proteins work at different stages in the DNA damage response (DDR) and in DNA repair. BRCA1 is a pleiotropic DDR protein that functions in both checkpoint activation and DNA repair, whereas BRCA2 is a mediator of the core mechanism of homologous recombination. The links between the two proteins are not well understood, but they must exist to explain the marked similarity of human cancer susceptibility that arises with germline mutations in these genes. As discussed here, the proteins work in concert to protect the genome from double-strand DNA damage during DNA replication.
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.
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.
Mutations in the BRCA genes increase the risk of breast cancer. Valid estimates of the magnitude of the lifetime risk of breast cancer in BRCA gene mutation carriers are needed for genetic counseling. Recent results suggest that penetrance has increased in recent birth cohorts. We examined the cumulative breast cancer incidence and mortality before age 70 over a diagnosis period of 80 years in Icelandic women who carried the BRCA2 founder mutation 999del5.
Information on all breast cancers diagnosed in Iceland since 1911 was obtained from the Icelandic Cancer Registry. Mutation status was determined by molecular analysis of tissue samples for 847 breast cancer probands who were diagnosed from 1921 through 1985 and selected without knowledge of family history of breast cancer. We estimated the cumulative incidence and mortality from breast cancer before age 70 years in BRCA2 mutation carriers from the observed risks in first-degree relatives who were classified according to mutation status of probands and followed-up through 2002. Poisson modeling of these risks was also carried out. All statistical tests were two-sided.
Of the 847 probands, 88 carried the BRCA2 999del5 mutation and 759 did not. According to Poisson modeling, the cumulative incidence of breast cancer before age 70 years in mutation carriers increased from 18.6% (95% CI = 11.0% to 29.5%) in calendar year 1920 to 71.9% (95% CI = 45.9% to 100%) in 2002 (P < .001); in relatives of probands who did not carry the BRCA2 mutation and in the general Icelandic population incidence increased over the same period from 2.6% to 10.7% and from 1.8% to 7.5%, respectively (all increases of approximately fourfold). During the same period, the cumulative risk of death from breast cancer before age 70 years for BRCA2 mutation carriers increased from 12.1% (95% CI = 5.3% to 23.9%) to 26.9% (95% CI = 10.9% to 55.5%) (P = .08). However, because the probands were breast cancer patients and not a random sample from the population, some bias in the estimation of time trends in penetrance cannot be ruled out.
The results indicate that the penetrance of the Icelandic BRCA2 founder mutation increased nearly fourfold in 80 years, whereas the risk of death from breast cancer before age 70 years increased only approximately twofold. Changes in penetrance with time should be considered when penetrance is estimated.
Aluminium (Al) has been measured in human breast tissue, and may be a contributory factor in breast cancer development. At the 10th Keele meeting, we reported that long-term exposure to Al could increase migratory properties of oestrogen-responsive MCF-7 human breast cancer cells suggesting a role for Al in the metastatic process. We now report that long-term exposure (20-25weeks) to Al chloride or Al chlorohydrate at 10(-4)M or 10(-5)M concentrations can also increase the migration of oestrogen unresponsive MDA-MB-231 human breast cancer cells as measured using time-lapse microscopy and xCELLigence technology. In parallel, Al exposure was found to give rise to increased secretion of active matrix metalloproteinase MMP9 as measured by zymography, and increased intracellular levels of activated MMP14 as measured by western immunoblotting. These results demonstrate that Al can increase migration of human breast cancer cells irrespective of their oestrogen responsiveness, and implicate alterations to MMPs as a potential mechanism worthy of further study.
Aluminium (Al) has been measured in human breast tissue, nipple aspirate fluid and breast cyst fluid, and recent studies have shown that at tissue concentrations, aluminium can induce DNA damage and suspension growth in human breast epithelial cells. This paper demonstrates for the first time that exposure to aluminium can also increase migratory and invasive properties of MCF-7 human breast cancer cells. Long-term (32weeks) but not short-term (1week) exposure of MCF-7 cells to 10(-4)M aluminium chloride or 10(-4)M aluminium chlorohydrate increased motility of the cells as measured by live cell imaging (cumulative length moved by individual cells), by a wound healing assay and by migration in real time through 8μm pores of a membrane using xCELLigence technology. Long-term exposure (37weeks) to 10(-4)M aluminium chloride or 10(-4)M aluminium chlorohydrate also increased the ability of MCF-7 cells to invade through a matrigel layer as measured in real time using the xCELLigence system. Although molecular mechanisms remain to be characterized, the ability of aluminium salts to increase migratory and invasive properties of MCF-7 cells suggests that the presence of aluminium in the human breast could influence metastatic processes. This is important because mortality from breast cancer arises mainly from tumour spread rather than from the presence of a primary tumour in the breast.
The aetiology of breast cancer is multifactorial. While there are known genetic predispositions to the disease it is probable that environmental factors are also involved. Recent research has demonstrated a regionally specific distribution of aluminium in breast tissue mastectomies while other work has suggested mechanisms whereby breast tissue aluminium might contribute towards the aetiology of breast cancer. We have looked to develop microwave digestion combined with a new form of graphite furnace atomic absorption spectrometry as a precise, accurate and reproducible method for the measurement of aluminium in breast tissue biopsies. We have used this method to test the thesis that there is a regional distribution of aluminium across the breast in women with breast cancer. Microwave digestion of whole breast tissue samples resulted in clear homogenous digests perfectly suitable for the determination of aluminium by graphite furnace atomic absorption spectrometry. The instrument detection limit for the method was 0.48μg/L. Method blanks were used to estimate background levels of contamination of 14.80μg/L. The mean concentration of aluminium across all tissues was 0.39μg Al/g tissue dry wt. There were no statistically significant regionally specific differences in the content of aluminium. We have developed a robust method for the precise and accurate measurement of aluminium in human breast tissue. There are very few such data currently available in the scientific literature and they will add substantially to our understanding of any putative role of aluminium in breast cancer. While we did not observe any statistically significant differences in aluminium content across the breast it has to be emphasised that herein we measured whole breast tissue and not defatted tissue where such a distribution was previously noted. We are very confident that the method developed herein could now be used to provide accurate and reproducible data on the aluminium content in defatted tissue and oil from such tissues and thereby contribute towards our knowledge on aluminium and any role in 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.
Parabens (alkyl esters of p-hydroxybenzoic acid) are used extensively as preservatives in consumer products, and intact esters have been measured in several human tissues. Concerns of a potential link between parabens and breast cancer have been raised, but mechanistic studies have centred on their oestrogenic activity and little attention has been paid to any carcinogenic properties. In the present study, we report that parabens can induce anchorage-independent growth of MCF-10A immortalized but non-transformed human breast epithelial cells, a property closely related to transformation and a predictor of tumour growth in vivo. In semi-solid methocel suspension culture, MCF-10A cells produced very few colonies and only of a small size but the addition of 5 × 10(-4) M methylparaben, 10(-5) M n-propylparaben or 10(-5) M n-butylparaben resulted in a greater number of colonies per dish (P < 0.05 in each case) and an increased average colony size (P < 0.001 in each case). Dose-responses showed that concentrations as low as 10(-6) M methylparaben, 10(-7) M n-propylparaben and 10(-7) M n-butylparaben could increase colony numbers (P = 0.016, P = 0.010, P = 0.008, respectively): comparison with a recent measurement of paraben concentrations in human breast tissue samples from 40 mastectomies (Barr et al., 2012) showed that 22/40 of the patients had at least one of the parabens at the site of the primary tumour at or above these concentrations. To our knowledge, this is the first study to report that parabens can induce a transformed phenotype in human breast epithelial cells in vitro, and further investigation is now justified into a potential link between parabens and breast carcinogenesis. Copyright © 2012 John Wiley & Sons, Ltd.
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.
Genomic instability is one of the most pervasive characteristics of tumour cells and is probably the combined effect of DNA damage, tumour-specific DNA repair defects, and a failure to stop or stall the cell cycle before the damaged DNA is passed on to daughter cells. Although these processes drive genomic instability and ultimately the disease process, they also provide therapeutic opportunities. A better understanding of the cellular response to DNA damage will not only inform our knowledge of cancer development but also help to refine the classification as well as the treatment of the disease.
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.
The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list-reprogramming of energy metabolism and evading immune destruction. In addition to cancer cells, tumors exhibit another dimension of complexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition of hallmark traits by creating the "tumor microenvironment." Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer.
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.
Unlabelled:
Many environmental compounds with oestrogenic activity are measurable in the human breast and oestrogen is a known factor in breast cancer development. Exposure to environmental oestrogens occurs through diet, household products and cosmetics, but concentrations of single compounds in breast tissue are generally lower than needed for assayable oestrogenic responses. Results presented here and elsewhere demonstrate that in combination, chemicals can give oestrogenic responses at lower concentrations, which suggests that in the breast, low doses of many compounds could sum to give a significant oestrogenic stimulus. Updated incidence figures show a continued disproportionate incidence of breast cancer in Britain in the upper outer quadrant of the breast which is also the region to which multiple cosmetic chemicals are applied.
Conclusion:
If exposure to complex mixtures of oestrogenic chemicals in consumer products is a factor in breast cancer development, then a strategy for breast cancer prevention could become possible.
If one was asked to produce a set of 'Trump Cards' based upon 'Forces of Nature Defining Life on Earth' then which card would be 'Top Trump'? I was recently chastised on the Darwin Today website for suggesting Darwin and 'natural selection' rather than, for example, Newton and 'gravity'. Although there is no denying the significance of gravity, my argument in favour of natural selection is simply that gravity is just one factor that contributes towards an outcome which ultimately is defined by natural selection. Both the beauty and the brilliance of natural selection are reflected in its omnipotence to explain the myriad observations of life and, as I will affirm herein, its explanation of the biological essentiality of aluminium and silicon is no exception.
Gross cystic breast disease (GCBD) is the most common benign breast disorder, but the molecular basis of cyst formation remains to be identified. If the use of aluminium-based antiperspirant salts is involved in the etiology of gross breast cyst formation, it might be expected that aluminium would be at elevated levels in human breast cyst fluid (BCF). Aluminium was measured by ICP-MS in 48 samples of BCF, 30 samples of human blood serum and 45 samples of human breast milk at different stages of lactation (colostrum, intermediate, mature). The median level of aluminium in apocrine type I BCF (n = 27, 150 microg l(-1)) was significantly higher than in transudative type II BCF (n = 21, 32 microg l(-1); P < 0.0001). By comparison, aluminium measurements gave a median concentration of 6 microg l(-1) in human serum and 25 microg l(-1) in human breast milk, with no difference between colostrum, intermediate and mature milk. Levels of aluminium were significantly higher in both types of BCF than in human serum (P < 0.0001). However when compared with human breast milk, aluminium levels were only significantly higher in apocrine type I BCF (P < 0.0001) and not in transudative type II BCF (P = 0.152). It remains to be identified why such high levels of aluminium were found in the apocrine type I BCF and from where the aluminium originated. However, if aluminium-based antiperspirants are found to be the source and to play any causal role in development of breast cysts, then it might become possible to prevent this common breast disorder.
Aluminium chlorohydrate (ACH), the active ingredient in many antiperspirants, was labeled with the radioisotope 26Al. The labeled ACH was then fractionated into about 100 samples using gel filtration chromatography. Each fraction was analyzed for 26Al and total aluminium content. Aluminium-26 was only detected in the fractions that also contained aluminium, which verified that the ACH was uniformly labeled. 84 mg of the labeled ACH was then applied to a single underarm of two adult subjects with blood and urine samples being collected over 7 weeks. Tape-stripping and mild washings of the skin were also collected for the first 6 days. Results indicate that only 0.012% of the applied aluminium was absorbed through the skin. At this rate, about 4 microg of aluminium is absorbed from a single use of ACH on both underarms. This is about 2.5% of the aluminium typically absorbed by the gut from food over the same time period. Therefore, a one-time use of ACH applied to the skin is not a significant contribution to the body burden of aluminium.
The rumor that antiperspirant use causes breast cancer continues to circulate the Internet. Although unfounded, there have
been no published epidemiologic studies to support or refute this claim. This population-based case– control study investigated
a possible relationship between use of products applied for underarm perspiration and the risk for breast cancer in women
aged 20–74 years. Case patients (n = 813) were diagnosed between November 1992 and March 1995; control subjects (n = 793)
were identified by random digit dialing and were frequency-matched by 5-year age groups. Product use information was obtained
during an in-person interview. Odds ratios (ORs) and 95% confidence intervals were estimated by the use of conditional logistic
regression. P values were determined with the Wald χ2 test. All statistical tests were two-sided. The risk for breast cancer did not increase with any of the following activities:
1) antiperspirant (OR = 0.9; P = .23) or deodorant (OR = 1.2; P = .19) use; 2) product use among subjects who shaved with a blade razor; or 3) application of products within 1 hour of shaving
(for antiperspirant, OR = 0.9 and P = .40; for deodorant, OR = 1.2 and P = .16). These findings do not support the hypothesis that antiperspirant use increases the risk for breast cancer.
The elaboration of biogeochemical cycles for elements which are known to be essential for life has enabled a broad appreciation of the homeostatic mechanisms which underlie element essentiality. In particular they can be used effectively to identify any part played by human activities in element cycling and to predict how such activities might impact upon the lithospheric and biospheric availability of an element in the future. The same criteria were the driving force behind the construction of a biogeochemical cycle for aluminium, a non-essential element which is a known ecotoxicant and a suspected health risk in humans. The purpose of this exercise was to examine the concept of a biogeochemical cycle for aluminium and not to review the biogeochemistry of this element. The cycle as presented is rudimentary and qualitative though, even in this nascent form, it is informative and predictive and, for these reasons alone, it is deserving of future quantification. A fully fledged biogeochemical cycle for aluminium should explain the biospheric abundance of this element and whether we should expect its (continued) active involvement in biochemical evolution.
Breast cancer incidence suggests a lifestyle cause. A lifestyle factor used near the breast is the application of antiperspirants/deodorants accompanied by axillary shaving. A previous study did not support a link with breast cancer. If these habits have a role in breast cancer development, women using antiperspirants/deodorants and shaving their underarms frequently would be expected to have an earlier age of diagnosis than those doing so less often. An earlier age of diagnosis would also be expected in those starting to use deodorants and shaving at an earlier age. This is the first study to investigate the intensity of underarm exposure in a cohort of breast cancer survivors. Four hundred and thirty-seven females diagnosed with breast cancer were surveyed. Once grouped by their frequency of underarm hygiene habits, the mean age of diagnosis was the primary end point. Secondary end points included the overall frequency of these habits, and potential usage group confounding variables were evaluated. All statistical tests were two-sided. Frequency and earlier onset of antiperspirant/deodorant usage with underarm shaving were associated with an earlier age of breast cancer diagnosis. Combined habits are likely for this earlier age of diagnosis. In conclusion, underarm shaving with antiperspirant/deodorant use may play a role in breast cancer. It is not clear which of these components are involved. Reviewed literature insinuates absorption of aluminium salts facilitated by dermal barrier disruption. Case-controlled investigations are needed before alternative underarm hygiene habits are suggested.
Although risk factors are known to include the loss of function of the susceptibility genes BRCA1/BRCA2 and lifetime exposure to oestrogen, the main causative agents in breast cancer remain unaccounted for. It has been suggested recently that underarm cosmetics might be a cause of breast cancer, because these cosmetics contain a variety of chemicals that are applied frequently to an area directly adjacent to the breast. The strongest supporting evidence comes from unexplained clinical observations showing a disproportionately high incidence of breast cancer in the upper outer quadrant of the breast, just the local area to which these cosmetics are applied. A biological basis for breast carcinogenesis could result from the ability of the various constituent chemicals to bind to DNA and to promote growth of the damaged cells. Multidisciplinary research is now needed to study the effect of long-term use of the constituent chemicals of underarm cosmetics, because if there proves to be any link between these cosmetics and breast cancer then there might be options for the prevention of breast cancer.
Theory holds that the upper outer quadrant of the breast develops more malignancies because of increased tissue volume. This study evaluated genomic patterns of loss of heterozygosity (LOH) and allelic imbalance (AI) in non-neoplastic tissues from quadrants of diseased breasts following mastectomy to characterize relationships between genomic instability and the propensity for tumor development.
Tissues from breast quadrants were collected from 21 patients with various stages of breast carcinoma. DNA was isolated from non-neoplastic tissues using standard methods and 26 chromosomal regions commonly deleted in breast cancer were examined to assess genomic instability.
Genomic instability was observed in breast quadrants from patients with ductal carcinomas in situ and advanced carcinomas. Levels of instability by quadrant were not predictive of primary tumor location (P =.363), but outer quadrants demonstrated significantly higher levels of genomic instability than did inner quadrants (P =.017). Marker D8S511 on chromosome 8p22-21.3, one of the most frequently altered chromosomal regions in breast cancer, showed a significantly higher level of instability (P =.039) in outer compared with inner quadrants.
Non-neoplastic breast tissues often harbor genetic changes that can be important to understanding the local breast environment within which cancer develops. Greater genomic instability in outer quadrants can partially explain the propensity for breast cancers to develop there, rather than simple volume-related concepts. Patterns of field cancerization in the breast appear to be complex and are not a simple function of distance from a developing tumor.
Breast cancer is an important contributor to morbidity and mortality in society, but factors that affect the cause of the disease are poorly defined. Genomic instability drives tumorigenic processes in invasive carcinomas and premalignant breast lesions, and might promote the accumulation of genetic alterations in apparently normal tissues before histological abnormalities are detectable. Evidence suggests that genomic changes in breast parenchyma affect the behaviour of epithelial cells, and ultimately might affect tumour growth and progression. Inherent instability in genes that maintain genomic integrity, as well as exogenous chemicals and environmental pollutants, have been implicated in breast-cancer development. Although molecular mechanisms of tumorigenesis are unclear at present, carcinogenic agents could contribute to fields of genomic instability localised to specific areas of the breast. Understanding the functional importance of genomic instability in early carcinogenesis has important implications for improvement of diagnostic and treatment strategies.
Although aluminum (Al) is responsible for the etiology of some human diseases, not much is known about the mechanisms of its genotoxic activity. The available data suggest that Al can induce DNA damage by modifying the structure of chromatin through the induction of reactive oxygen species or by damaging lysosomal membranes and liberating DNase. We treated human peripheral-blood lymphocytes with AlCl3 in the G0/G1 phase, in the S/G2 phase, and during the whole cell cycle. The aim of the study was to check if the sensitivity of lymphocytes to Al varied through the cell cycle. A high sensitivity in the S phase would point toward chromatin modification as the major source of DNA damage. Micronuclei (Mn) and apoptosis were assessed as the end points. Cells were treated with 1, 2, 5, 10, and 25 microg/mL AlCl3. Mn induced by 5 microg/mL of AlCl3 were analyzed by FISH for centromeric signal content. After all treatment schemes the frequency of Mn increased initially, but decreased at high AlCl3 concentrations. This drop of Mn frequency could be explained by a strong increase in the frequency of apoptosis. AlCl3 induced both Mn with and without centromeres. The G0/G1 phase of the cell cycle was found to be more sensitive than were the S and G2 phases. This points toward oxidative stress or liberation of DNase as the major source of DNA damage induced by Al.