Arsenite stimulates poly(ADP-ribosylation) by generation of nitric oxide.
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 nitric oxide may be important to the etiology of arsenic-induced vascular disorders in humans.
Lynn
S
S
Institute of Zoology, Academia Sinica, Taipei, Taiwan, ROC.
Shiung
J N
JN
Gurr
J R
JR
Jan
K Y
KY
D000818:Animals; D001011:Aorta; D018053:Arsenites / Q000494:pharmacology*; D016466:CHO Cells; D002374:Catalase / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002417:Cattle; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D002478:Cells, Cultured; D006224:Cricetinae; D004249:DNA Damage; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D009243:NAD / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009573:Nitrites / Q000378:metabolism; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013723:Teratogens / Q000494:pharmacology*
D018053:Arsenites; D004791:Enzyme Inhibitors; D009573:Nitrites; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D013723:Teratogens; D009243:NAD; D011064:Poly Adenosine Diphosphate Ribose; D009569:Nitric Oxide; D002374:Catalase; D019001:Nitric Oxide Synthase; D011065:Poly(ADP-ribose) Polymerases; C015001:arsenite