Genomic Instability Is an Early Event in Aluminium-Induced Tumorigenesis.
Mandriota SJ., Tenan M., Nicolle A., Jankowska JD., Ferrari P., Tille J-C., Durin M-A., Green CM., Tabruyn S., Moralli D., Sappino A-P.
Genomic instability is generally considered as a hallmark of tumorigenesis and a prerequisite condition for malignant transformation. Aluminium salts are suspected environmental carcinogens that transform mammary epithelial cells in vitro through unknown mechanisms. We report here that long-term culture in the presence of aluminium chloride (AlCl<sub>3</sub>) enables HC11 normal mouse mammary epithelial cells to form tumours and metastases when injected into the syngeneic and immunocompetent BALB/cByJ strain. We demonstrate that AlCl<sub>3</sub> rapidly increases chromosomal structural abnormalities in mammary epithelial cells, while we failed to detect direct modulation of specific mRNA pathways. Our observations provide evidence that clastogenic activity-a well-recognized inducer of genomic instability-might account in part for the transforming abilities of aluminium in mammary epithelial cells.