en
Scientific article
Open access
English

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

Published inJAT. Journal of applied toxicology, vol. 32, no. 3, p. 233-243
Publication date2012
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 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.

Keywords
  • Aluminum Compounds/toxicity
  • Antiperspirants/toxicity
  • Breast/drug effects/pathology
  • Cell Line, Tumor
  • Cell Proliferation/drug effects
  • Cell Transformation, Neoplastic
  • Chlorides/toxicity
  • DNA Breaks, Double-Stranded
  • DNA Repair
  • Epithelial Cells/drug effects
  • Female
  • Humans
Citation (ISO format)
SAPPINO, André-Pascal et al. Aluminium chloride promotes anchorage-independent growth in human mammary epithelial cells. In: JAT. Journal of applied toxicology, 2012, vol. 32, n° 3, p. 233–243. doi: 10.1002/jat.1793
Main files (1)
Article (Published version)
accessLevelPublic
Identifiers
ISSN of the journal0260-437X
647views
622downloads

Technical informations

Creation09/29/2014 1:24:00 PM
First validation09/29/2014 1:24:00 PM
Update time03/14/2023 9:48:28 PM
Status update03/14/2023 9:48:27 PM
Last indexation01/16/2024 11:58:25 AM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack