Aluminium chloride promotes anchorage‐independent growth in human mammary epithelial cells

Abstract

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 mM, 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/p21Waf1 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.

Systematic review of potential health risks posed by pharmaceutical, occupational and consumer exposures to metallic and nanoscale aluminum, aluminum oxides, aluminum hydroxide and its soluble salts

“…Sappino et al (2012) investigated 0, 10, 100 or 300 μM AlCl 3 or ACH (purity ≥ 99%) in cultured MCF-10A cells and in cultured human primary mammary epithelial cells. Sappino et al (2012) suggested that “at the expected pH of the cell culture medium (pH ~7.2), AlCl 3 and ACH yield the same dissociation product, aluminum hydroxide”.…”

Biological Water Dynamics and Entropy: A Biophysical Origin of Cancer and Other Diseases

“…Silva et al (2012) found that the following metals were capable of binding to cellular estrogen receptors and then mimicking the actions of physiological estrogens: "aluminium, antimony, arsenite, barium, cadmium, chromium (Cr(II)), cobalt, copper, lead, mercury, nickel, selenite, tin and vanadate" [296,297]. Al has recently been identified in breast cancer tissue [298,299], with a significantly higher concentration in the upper outer quadrant of the breast than in the inner (middle and medial) regions. In 2012, Sappino et al [299] found that, in MCF-10A human mammary epithelial cells, a well-established normal human mammary epithelial cell model, long-term exposure to aluminum chloride (AlCl 3 ) concentrations of 10-300 μM, i.e.…”

“…Al has recently been identified in breast cancer tissue [298,299], with a significantly higher concentration in the upper outer quadrant of the breast than in the inner (middle and medial) regions. In 2012, Sappino et al [299] found that, in MCF-10A human mammary epithelial cells, a well-established normal human mammary epithelial cell model, long-term exposure to aluminum chloride (AlCl 3 ) concentrations of 10-300 μM, 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.…”

“…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. This finding should serve as a sentinel warning that environmental Al exposures [252] from dietary [300], parenteral [301], and topical sources [302], may have oncogenic [299,303] and epigenetic [245,253] consequences.…”

Prostatic Tissue Levels of 43 Trace Elements in Patients with Prostate Adenocarcinoma

“…On the other hand, findings of this study documented fact that the adenocarcinoma of human prostate accumulates high levels of many trace elements including Al, B, Be, Bi, Cr, Fe, Hg, Ni, Sn, Th, and Zr. Genotoxicity and carcinogenicity of these elements are well known (Anghileri et al, 2000;Gordon & Bowser, 2003;Crespo-López et al, 2009;Bian et al, 2011;Gonzalez-Vasconcellos et al, 2011;Müezzinoğlu et al, 2011;Sappino et al, 2012;Helmig et al, 2013;Adámik et al, 2015;Farasani & Darbre, 2015). On the other hand, compared to human body soft tissues, the normal prostate of young adults has higher levels of many trace elements, including Zn (V. Zaichick & S. Zaichick, 2013, 2013a, 2013b, 2013c, 2014d.…”