Metabolites of arsenic induced tetraploids and mitotic arrest in cultured cells.

The toxic effects of arsenic compounds on cell divisionwere studied, using Chinese hamster V79 cells. Seven arsenic compounds weretested. Inorganic arsenic compounds (arsenite and arsenate), which have beenfound in drinking water, inhibited cell growth at very low concentrations. Monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and trimethylarsineoxide (TMAO), which are methylated metabolites of inorganic arsenics, wereless cytotoxic than the inorganic arsenics themselves. The cytotoxicity ofthe three methylated metabolites decreased as the number of methyl groupsincreased. Arsenobetaine (AsBe) and arsenocholine (AsC), which have beenfound in some marine products, did not show any cytotoxicity. Threemethylated metabolites; MMA, DMA and TMAO induced mitotic arrest. Tetraploidyproduction was observed in cells exposed to DMA or TMAO. Arsenite, arsenate,AsBe and AsC did not induce mitotic arrest or tetraploids. These resultssuggest that MMA, DMA and TMAO exert some effect on cell division inmetaphase and may thereby give some clue as to the carcinogenic mechanism ofarsenic.