Fragmentation of the DNA Repair Enzyme, OGG1, in Mouse Nonparenchymal Liver Cells by Arsenic Compounds

[摘要] References(28)Cited-By(9)Our previous work demonstrated that arsenic compounds increased 8-hydroxyguanine (8-OH-Gua) in the DNA of cultured human cells (A549) and reduced the endonuclease nicking activity for 8-OH-Gua, suggesting that arsenic compound-induced carcinogenesis was the consequence of the inhibition of DNA repair. However, the exact mechanism by which the repair systems were disturbed was unknown. To elucidate the mechanism, we analyzed mouse 8-oxoguanine DNA glycosylase 1 (mOGG1) expression in mouse nonparenchymal liver cells, NCTC, treated with arsenic compounds (arsenic trioxide, sodium arsenite, and sodium hydrogen arsenate). We detected a cleaved form of mOGG1 (35 kDa) in addition to normal mOGG1 (type 1a, 38 kDa) in NCTC treated with arsenic compounds. These results are similar to our previous results which showed that fragmentation of mOGG1 by etoposide was related to caspase-dependent apoptosis, and was accompanied by increased 8-OH-Gua accumulation. Taken together, our results suggested that arsenic compounds might increase 8-OH-Gua accumulation by inhibiting 8-OH-Gua repair, due to mOGG1 cleavage.

[学科分类] 分子生物学，细胞生物学和基因

[关键词] mOGG1;arsenic compounds;8-hydroxyguanine