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 promye-locytic leukemia NB4 cells with 0.5mM 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 xeroderma pigmentosum (XP) A, XPD, and XPG, excised Ultraviolet C-induced adducts less rapidly than normal fibroblasts, but excise