PMID: 9438557Jan 23, 1998Paper

Arsenite stimulates poly(ADP-ribosylation) by generation of nitric oxide

Free Radical Biology & Medicine
S LynnK Y Jan

Abstract

Recent studies indicate that arsenic may generate reactive oxygen species to exert its toxicity. Because reactive oxygen species are known to induce poly(ADP-ribosylation), which is implicated in DNA repair, signal transduction, and apoptosis, we have investigated the effect of arsenite on poly(ADP-ribosylation). The results showed that arsenite treatment induced poly(ADP-ribosylation), NAD depletion, DNA strand breaks, and micronuclei in CHO-K1 cells. Increase of nitrite level, a stable product of nitric oxide, was also detected in medium of arsenite-treated cultures. S-methyl-L-thiocitrulline and N omega-nitro-L-arginine methyl ester, inhibitors of nitric oxide synthase, could suppress the arsenite-induced NAD depletion, DNA strand breaks, and micronuclei, whereas 3-aminobenzamide, an inhibitor of poly (ADP-ribose) polymerase, could enhance micronucleus production and NAD depletion in arsenite-treated cells. These results suggest that arsenite treatment may generate nitric oxide to damage DNA and which then stimulate poly(ADP-ribosylation). Because arsenite also induced DNA strand breaks and NAD depletion in bovine aortic endothelial cells, and these could also be suppressed by S-methyl-L-thiocitrulline, the induction of nitr...Continue Reading

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