Genotoxicity of dimethylarsinous acid: high induction of tetraploids

Arsenic is a carcinogen in humans. However, neither the mechanism of action nor the ultimate chemical form of arsenic which causes cancer has been clearly defined. Dimethylarsinous acid is detected in the urine of individuals who ingest arsenic-polluted drinking water. The cytogenetic study in V79 cells using iododimethylarsine, which is easily hydrolyzed to dimethylarsinous acid in water, revealed that dimethylarsinous acid was very cytotoxic (50% growth inhibition concentration; 1.1 ± 0.14 μM), and either induced aneuploids or a high rate of tetraploids (73% at 2.5 μM). Dimethylarsinous acid caused mitotic arrest, since the mitotic index at toxic dose (5 μM) was 13.9%, significantly higher than the control (2.7%). Dimethylarsinous acid significantly increased sister chromatid exchange (SCE) and chromosomal aberrations, most of which were chromatid gaps and chromatid breaks. The cytotoxicity and the activity of dimethylarsinous acid in inducing chromosomal aberration or SCE was as effective as arsenite, but the activity was much lower than that of mitomycin C, which was used as a positive control. The most potent effects of dimethylarsinous acid on the cells were induction of aneuploids, tetraploids and c-mitosis. Our results suggest that toxicity of dimethylarsinous acid is strongly related to the disturbance of the normal cell cycle.