Journal Article

Arsenic-induced DNA hypomethylation affects chromosomal instability in mammalian cells

Giulia Sciandrello, Fabio Caradonna, Maurizio Mauro and Giusi Barbata

in Carcinogenesis

Volume 25, issue 3, pages 413-417
Published in print March 2004 | ISSN: 0143-3334
Published online March 2004 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgh029
Arsenic-induced DNA hypomethylation affects chromosomal instability in mammalian cells

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Early genetic instability induced in dividing V79-Cl3 Chinese hamster cells by inorganic arsenic, as demonstrated in our previous investigation, was evidenced by aneuploidy and nuclear abnormalities, but not by chromosomal rearrangements. Here we report the results of cytogenetic and morphological analyses performed on the progeny of cells dividing at the end of sodium arsenite treatment after they had been expanded through 120 generations (ASO cells) and then cloned. The acquired genetic instability persisted and was increased by highly unstable chromosomal rearrangements, namely dicentric chromosomes and telomeric associations, which were not seen following acute exposure. A peculiar finding was the preferential involvement of a particular chromosome in dicentric rearrangements observed in some isolated ASO clones. Interestingly, by immunostaining with anti-5-methylcytosine antibodies the genome-wide DNA hypomethylation, induced by arsenic immediately after the acute treatment, was found to affect those ASO clones characterized by aneuploidy and chromosomal rearrangements. These findings demonstrate that short-term exposure to arsenic has long-term effects and suggest that genome-wide DNA hypomethylation enhances genetic instability.

Keywords: 5-MeC, 5-methylcytosine; SA, sodium arsenite

Journal Article.  2855 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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