OGG1 and MYH are involved in the incision of trivalent arsenical-induced DNA adducts.
Since trivalent arsenicals are known to induce oxidative DNA damage in human cells, we asked if they induce other types of DNA damage and how these DNA damages are repaired. Treatment of human promyelocytic leukemia NB4 cells with 0.5 microM As2O3 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 H2O2-Fe treated nuclei or As2O3-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 XPA, XPD, and XPG, excised UVC-induced adducts less rapidly than normal fibroblasts, but excised As2O3-adducts at the same rate as the normal cells. Immunodepletion of the NE with antibody against OGG1 or MYH decreased the incision of DNA adducts induced by As2O3, NaAsO2, monomethylarsonic acid, and dimethylarsinic acid, while antibodies against XPA, XPB, XPD, XPF, or XPG, did not. These results suggest that these trivalent arsenicals induce the formation of only oxidative DNA adducts and that OGG1 and MYH are involved in these incision processes.
Pu
Yeong-Shiau
YS
Department of Urology, National Taiwan University College of Medicine, Taipei, Taiwan, ROC.
Jan
Kun-Yan
KY
Wang
Tsing-Cheng
TC
Wang
Alexander S S
AS
Gurr
Jia-Ran
JR