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Chromosome instability (CIN) consists of high rates of structural and numerical chromosome abnormalities and is a well-known hallmark of cancer. Aluminum is added to many industrial products of frequent use. Yet, it has no known physiological role and is a suspected human carcinogen. Here, we show that V79 cells, a well-established model for the evaluation of candidate chemical carcinogens in regulatory toxicology, when cultured in presence of aluminum-in the form of aluminum chloride (AlCl3) and at concentrations in the range of those measured in human tissues-incorporate the metal in a dose-dependent manner, predominantly accumulating it in the perinuclear region. Intracellular aluminum accumulation rapidly leads to a dose-dependent increase in DNA double strand breaks (DSB), in chromosome numerical abnormalities (aneuploidy) and to proliferation arrest in the G2/M phase of the cell cycle. During mitosis, V79 cells exposed to aluminum assemble abnormal multipolar mitotic spindles and appear to cluster supernumerary centrosomes, possibly explaining why they accumulate chromosome segregation errors and damage. We postulate that chronic aluminum absorption favors CIN in mammalian cells, thus promoting carcinogenesis.

Original publication

DOI

10.3390/ijms22179515

Type

Journal article

Journal

Int J Mol Sci

Publication Date

01/09/2021

Volume

22

Keywords

aluminium, lumogallion, metal, Aluminum, Aluminum Chloride, Animals, Cell Line, Centromere, Chromosomal Instability, Chromosomes, Mammalian, Cricetulus, DNA Breaks, Double-Stranded, G2 Phase Cell Cycle Checkpoints, M Phase Cell Cycle Checkpoints