Present address: Clinique des Grangettes, Chemin des Grangettes 7, 1224 Chêne-Bougeries, Switzerland.
Aluminium chloride promotes anchorage-independent growth in human mammary epithelial cells
Version of Record online: 6 JAN 2012
Copyright © 2012 John Wiley & Sons, Ltd.
Journal of Applied Toxicology
Volume 32, Issue 3, pages 233–243, March 2012
How to Cite
Sappino, A.-P., Buser, R., Lesne, L., Gimelli, S., Béna, F., Belin, D. and Mandriota, S. J. (2012), Aluminium chloride promotes anchorage-independent growth in human mammary epithelial cells. J. Appl. Toxicol., 32: 233–243. doi: 10.1002/jat.1793
- Issue online: 29 JAN 2012
- Version of Record online: 6 JAN 2012
- Manuscript Revised: 17 NOV 2011
- Manuscript Accepted: 17 NOV 2011
- Manuscript Received: 19 JUL 2011
- Ligue Genevoise contre le Cancer
- Fondation pour la Lutte contre le Cancer et pour des Recherches Médico-Biologiques
- Fondation André et Cyprien; the Fondation Prévot
- Fondation Meyer
- breast carcinogenesis;
- mammary epithelial cells;
- cellular transformation;
- cellular senescence
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.