Glutathione peroxidase and catalase modulate the genotoxicity of arsenite.
The X-ray hypersensitive Chinese hamster ovary (CHO) cells, xrs-5, are also more sensitive to sodium arsenite in terms of cell growth and micronucleus induction than CHO-K1 cells. Since reactive oxygen species are suggested to be involved in arsenic toxicity, we have measured antioxidant mechanisms in xrs-5 as well as CHO-K1 cells. There were no apparent differences in the activities of superoxide dismutase, glutathione S-transferase, glutathione reductase, and the levels of glutathione between xrs-5 and CHO-K1 cells. However, the activities of glutathione peroxidase and catalase were 5.4- and 5.8-fold lower, respectively, in xrs-5 cells. The addition of catalase or glutathione peroxidase to cultures reduced the arsenite-induced micronuclei in xrs-5 cells. Whereas, simultaneous treatment with mercaptosuccinate, an inhibitor of glutathione peroxidase, and 3-aminotriazole, an inhibitor of catalase, synergistically increased the arsenite-induced micronuclei. These results suggest that both catalase and glutathione peroxidase are involved in defense against arsenite genotoxicity. The xrs-6 cells, another line of x-ray hypersensitive CHO cells, which had 1.6-fold higher catalase activity and 2.5-fold higher glutathione peroxidase activity than xrs-5 cells, were also more sensitive than CHO-K1 cells but were less sensitive than xrs-5 cells to cell growth inhibition of arsenite. Moreover, a 1.6-fold increase of glutathione peroxidase activity by selenite adaptation effectively removed the arsenite-induced micronuclei in CHO-K1 cells. These results suggest that glutathione peroxidase is more important than catalase in defending against arsenite toxicity. Our results also suggest that increasing the intracellular antioxidant level may have preventive or therapeutic effects in arsenic poisoning.
Wang
T S
TS
Institute of Radiation Biology, Tsing Hua University, Hsinchu, Taiwan, Republic of China.
Shu
Y F
YF
Liu
Y C
YC
Jan
K Y
KY
Huang
H
H
D000640:Amitrole / Q000633:toxicity; D000818:Animals; D018053:Arsenites / Q000633:toxicity*; D016466:CHO Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000528:radiation effects; D002273:Carcinogens / Q000633:toxicity; D002374:Catalase / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D006224:Cricetinae; D004249:DNA Damage; D004357:Drug Synergism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000235:genetics; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism*; D005980:Glutathione Reductase / Q000235:genetics / Q000378:metabolism; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D015162:Micronucleus Tests; D017670:Sodium Compounds / Q000633:toxicity*; D013439:Sulfhydryl Reagents / Q000008:administration & dosage / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D013870:Thiomalates / Q000633:toxicity
D018053:Arsenites; D002273:Carcinogens; D017670:Sodium Compounds; D013439:Sulfhydryl Reagents; D013870:Thiomalates; C017947:sodium arsenite; C046062:2-thiomalic acid; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D000640:Amitrole