Genomic Instability Is an Early Event in Aluminium-Induced Tumorigenesis

Author:

Mandriota Stefano J.,Tenan Mirna,Nicolle AdelineORCID,Jankowska Julia D.,Ferrari Paolo,Tille Jean-ChristopheORCID,Durin Mary-AnneORCID,Green Catherine M.,Tabruyn SebastienORCID,Moralli DanielaORCID,Sappino André-Pascal

Abstract

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 (AlCl3) 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 AlCl3 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.

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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