8-Oxoguanine DNA glycosylase and MutY homolog are involved in the incision of arsenite-induced DNA adducts.
Since arsenite is known to induce oxidative DNA damage in human cells, we asked if it induces other types of DNA damage and how the DNA damage is repaired. Treatment of human promyelocytic leukemia NB4 cells with 0.5muM As(2)O(3) for 30 min induced no DNA breaks, as analyzed by a standard comet assay. However, breaks were detected if these cells were then digested with endonuclease III (EnIII), formamidopyrimidine-DNA glycosylase (Fpg), or a nuclear extract (NE) of NB4 cells. Using either H(2)O(2)-Fe-treated nuclei or As(2)O(3)-treated cells, digestion with either NE or EnIII + Fpg generated the same amount of breaks, and subsequent treatment with EnIII + Fpg resulted in no increase in breaks in NE-digested cells and vice versa. The human cell lines, defective in nucleotide excision protein, such as xeroderma pigmentosum (XP) A, XPD, and XPG, excised Ultraviolet C-induced adducts less rapidly than normal fibroblasts, but excised As(2)O(3) adducts at the same rate as the normal cells. Immunodepletion of the NE with antibody against 8-oxoguanine DNA glycosylase (OGG1) or MutY homolog (MYH) decreased the incision of As(2)O(3)-induced adducts, while antibodies against XPA, XPB, XPD, XPF, or XPG, did not. These results suggest that As(2)O(3) induces the formation of only oxidative DNA adducts and that OGG1 and MYH are involved in this incision process.
Pu
Yeong-Shiau
YS
Department of Urology, National Taiwan University College of Medicine, Taipei 10002, Taiwan, ROC.
Jan
Kun-Yan
KY
Wang
Tsing-Cheng
TC
Wang
Alexander S S
AS
Gurr
Jia-Ran
JR
D000077237:Arsenic Trioxide; D001152:Arsenicals; D002460:Cell Line; D020552:Comet Assay; D018736:DNA Adducts / Q000378:metabolism*; D004249:DNA Damage; D045647:DNA Glycosylases / Q000378:metabolism*; D004260:DNA Repair; D004785:Environmental Pollutants / Q000633:toxicity*; D005296:Ferrous Compounds / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D010087:Oxides / Q000633:toxicity*
D001152:Arsenicals; D018736:DNA Adducts; D004785:Environmental Pollutants; D005296:Ferrous Compounds; D010087:Oxides; C020748:ferrous sulfate; D006861:Hydrogen Peroxide; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase; C479058:oxoguanine glycosylase 1, human; D000077237:Arsenic Trioxide