DNA-Strand Breaks Induced by Dimethylarsinic Acid, a Metabolite of Inorganic Arsenics, Are Strongly Enhanced by Superoxide Anion Radicals

Abstract

We previously reported that dimethylarsinic acid (DMAA), a major metabolite of inorganic arsenics, induced DNA single-strand breaks (ssb) both in vivo and in cultured alveolar type II (L-132) cells in vitro, possibly via the production of dimethylarsenic peroxyl radicals. Here, the interaction of superoxide anion radicals (O-2) in the induction of ssb in L-132 cells was investigated using paraquat, an O-2-producing agent. A significant enhancement of ssb formation was observed in the DMAA-exposed cells when coexposed to paraquat. This enhancement occurred even when post-exposed to DMAA after washing, suggesting that the DMAA exposure caused some modification of DNA such as DNA-adducts, which was recognized by active oxygens to form ssb. An experiment with UV-irradiation, which was likely to induce ssb at the modified region, supported the possibility of DNA modification by DMAA exposure. An ESR study indicated that O-2 produced by paraquat in DMAA-exposed cells was more consumed than in non-exposed cells, assumingly through the reaction with the dimethylarsenic-modified region of DNA. The species of active oxygens were estimated by using diethyldithiocarbamate, aminotriazole, diethylmaleate, hydrogen peroxide (H2O2), γ-irradiation and ethanol. O-2 but neither H2O2 nor hydroxyl radicals was very likely to contribute to the ssb-enhancing action of paraquat. © 1995, The Pharmaceutical Society of Japan. All rights reserved.