Aluminium chloride promotes anchorage-independent growth in human mammary epithelial cells.
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.
Division of Oncology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
André-Pascal
AP
Sappino
Raphaële
R
Buser
Laurence
L
Lesne
Stefania
S
Gimelli
Frédérique
F
Béna
Dominique
D
Belin
Stefano J
SJ
Mandriota
D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000633:toxicity*; D051520:Antiperspirants / Q000633:toxicity*; D001940:Breast / Q000187:drug effects* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D002712:Chlorides / Q000633:toxicity*; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004847:Epithelial Cells / Q000187:drug effects; D005260:Female; D006801:Humans
D017607:Aluminum Compounds; D051520:Antiperspirants; D002712:Chlorides; D000077410:Aluminum Chloride