title: Aluminium chloride promotes tumorigenesis and metastasis in normal murine mammary gland epithelial cells.
abstract: Aluminium salts, present in many industrial products of frequent use like antiperspirants, anti-acid drugs, food additives and vaccines, have been incriminated in contributing to the rise in breast cancer incidence in Western societies. However, current experimental evidence supporting this hypothesis is limited. For example, no experimental evidence that aluminium promotes tumorigenesis in cultured mammary epithelial cells exists. We report here that long-term exposure to concentrations of aluminium-in the form of aluminium chloride (AlCl3)-in the range of those measured in the human breast, transform normal murine mammary gland (NMuMG) epithelial cells in vitro as revealed by the soft agar assay. Subcutaneous injections into three different mouse strains with decreasing immunodeficiency, namely, NOD SCID gamma (NSG), NOD SCID or nude mice, revealed that untreated NMuMG cells form tumors and metastasize, to a limited extent, in the highly immunodeficient and natural killer (NK) cell deficient NSG strain, but not in the less permissive and NK cell competent NOD SCID or nude strains. In contrast, NMuMG cells transformed in vitro by AlCl3form large tumors and metastasize in all three mouse models. These effects correlate with a mutagenic activity of AlCl3. Our findings demonstrate for the first time that concentrations of aluminium in the range of those measured in the human breast fully transform cultured mammary epithelial cells, thus enabling them to form tumors and metastasize in well-established mouse cancer models. Our observations provide experimental evidence that aluminium salts could be environmental breast carcinogens.
authors.affiliation: Center of Oncology, Faculty of Medicine, University of Geneva, Switzerland. stefano.mandriota@fondation.grangettes.ch.|Laboratoire de cancérogenèse environnementale, Fondation des Grangettes, Chêne-Bougeries, Switzerland. stefano.mandriota@fondation.grangettes.ch.
authors.forename: Stefano J
authors.identifier: http://orcid.org/0000-0001-6071-4804
authors.initials: SJ
authors.lastname: Mandriota
authors.affiliation: Laboratoire de cancérogenèse environnementale, Fondation des Grangettes, Chêne-Bougeries, Switzerland.
authors.forename: Mirna
authors.initials: M
authors.lastname: Tenan
authors.affiliation: Laboratoire de cancérogenèse environnementale, Fondation des Grangettes, Chêne-Bougeries, Switzerland.
authors.forename: Paolo
authors.initials: P
authors.lastname: Ferrari
authors.affiliation: Center of Oncology, Faculty of Medicine, University of Geneva, Switzerland.|Laboratoire de cancérogenèse environnementale, Fondation des Grangettes, Chêne-Bougeries, Switzerland.|Clinique des Grangettes, Chêne-Bougeries, Switzerland.
authors.forename: André-Pascal
authors.initials: AP
authors.lastname: Sappino
mesh_terms: D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D002712:Chlorides / Q000494:pharmacology*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D008175:Lung Neoplasms / Q000556:secondary; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009362:Neoplasm Metastasis; D023041:Xenograft Model Antitumor Assays
chemical_list: D017607:Aluminum Compounds; D002712:Chlorides; D000077410:Aluminum Chloride
keywords: aluminium; antiperspirants; breast cancer; carcinogen; metastasis; mouse models of cancer