Early and late effects of arsenic exposure in mammalian cells

Previously we demonstrated that V79 Chinese hamster cells underwent either early genetic instability or apoptosis When exposed to sodium arsenite (SA). Genetic instability was evidenced by aneuploid and morphologically abnormal cells, but not by cells with chromosome aberrations. As dividing cells turned out to be the most sensitive to SA exposure, due to the arsenics direct action on the mitotic spindle assembly, we later ascertained the fate of genetically unstable cells escaping apoptosis, by harvesting mitotic rounded-up cells at the end of a 24 h treatment. The progeny of the exposed Chinese hamster cells showed an increased level of mutations related to genome DNA hypomethylation induced by arsenic after treatment. In fact, cytogenetic, morphological and molecular investigations, performed at several time points during the expanded growth in drug-free medium, emphasized that genomic instability reappeared since 60th cell generation. Metaphases with dicentric chromosomes or telomeric associations characterized cell population since 90th cell generation. Some of the isolated clones also bearing chromosomal end-to-end fusions maintained telomerase activity and were capable to proliferate accumulating genomic instability as well as transformed phenotype and spontaneous increased gene mutation oxidative stress associated. On the whole, these results raise the possibility that the short-term exposure to arsenic induces altered DNA methylation pattern conferring a selective advantage to cell variants. Similarly to Karpinets and Foy hypothesis (Carcinogenesis, 2005) we believe these unstable cells epigenetically reprogram their genome and proliferate in an error-prone mode