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

Authors

  • André-Pascal Sappino,

    1. Division of Oncology, Faculty of Medicine, University of Geneva, Geneva, Switzerland
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    • Present address: Clinique des Grangettes, Chemin des Grangettes 7, 1224 Chêne-Bougeries, Switzerland.

  • Raphaële Buser,

    1. Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland
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    • Present address: Faculty of Medicine, Department of Pediatrics, Division of Onco-Hematology, CANSEARCH Foundation, Avenue de la Roseraie 64, 1205 Geneva, Switzerland.

  • Laurence Lesne,

    1. Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland
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    • Present address: Faculty of Medicine, Department of Pediatrics, Division of Onco-Hematology, CANSEARCH Foundation, Avenue de la Roseraie 64, 1205 Geneva, Switzerland.

  • Stefania Gimelli,

    1. Service of Genetic Medicine, University Hospital of Geneva, Geneva, Switzerland
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  • Frédérique Béna,

    1. Service of Genetic Medicine, University Hospital of Geneva, Geneva, Switzerland
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  • Dominique Belin,

    1. Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland
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  • Stefano J. Mandriota

    Corresponding author
    • Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland
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    • Present address: Faculty of Medicine, Department of Pediatrics, Division of Onco-Hematology, CANSEARCH Foundation, Avenue de la Roseraie 64, 1205 Geneva, Switzerland.


S. J. Mandriota, Faculty of Medicine, Department of Pediatrics, Division of Onco-Hematology, CANSEARCH Foundation, Avenue de la Roseraie 64, 1205 Geneva, Switzerland.

E-mail: stefano.mandriota@unige.ch

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 (AlCl3) 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. AlCl3 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 AlCl3 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 AlCl3 generates and selects for cells able to bypass p53/p21Waf1-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. Copyright © 2012 John Wiley & Sons, Ltd.

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