DNA-strand breaks induced by dimethylarsinic acid, a metabolite of inorganic arsenics, are strongly enhanced by superoxide anion radicals.
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 (O2-) in the induction of ssb in L-132 cells was investigated using paraquat, an O2(-)-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 O2- 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), gamma-irradiation and ethanol. O2- but neither H2O2 nor hydroxyl radicals was very likely to contribute to the ssb-enhancing action of paraquat.
Rin
K
K
School of Pharmaceutical Sciences, University of Shizuoka, Japan.
Kawaguchi
K
K
Yamanaka
K
K
Tezuka
M
M
Oku
N
N
Okada
S
S
D002101:Cacodylic Acid / Q000633:toxicity*; D002478:Cells, Cultured; D004249:DNA Damage / Q000187:drug effects*; D004277:DNA, Single-Stranded / Q000187:drug effects*; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D010269:Paraquat / Q000633:toxicity; D013481:Superoxides / Q000494:pharmacology*
D004277:DNA, Single-Stranded; D013481:Superoxides; D002101:Cacodylic Acid; D010269:Paraquat