Oxidative DNA adducts and DNA-protein cross-links are the major DNA lesions induced by arsenite

被引:82
作者
Bau, DT
Wang, TS
Chung, CH
Wang, ASS
Jan, KY [1 ]
机构
[1] Acad Sinica, Inst Zool, Taipei 11529, Taiwan
[2] Natl Def Med Ctr, Grad Inst Life Sci, Taipei, Taiwan
[3] Chung Shan Med & Dent Univ, Dept Life Sci, Taichung, Taiwan
关键词
arsenic; comet assay; DNA damage; hypochlorous acid; nitric oxide; peroxynitrite; thymine glycol; reactive oxygen species;
D O I
10.1289/ehp.02110s5753
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
Arsenic is recognized to be nonmutagenic carcinogen because it induces DNA damage only at very high concentrations. However, many more DNA strand breaks could be detected by digesting the DNA of arsenite-treated cells with endonuclease III, formamidopyrimidine-DNA glycosylase, and proteinase K. By doing so, arsenite could be shown to induce DNA damage in human cells within a pathologically meaningful concentration range. Oxidized guanine products were detected in all arsenite-treated human cells examined. DNA-protein cross-links were also detected in arsenite-treated NB4 and HL60 cells. In human umbilical vein endothelial cells, the induction of oxidized guanine products by arsenite was sensitive to inhibitors of nitric oxide (NO) synthase but not to oxidant modulators, whereas the opposite result was obtained in vascular smooth muscle cells. On the other hand, the arsenite-induced oxidized guanine products and DNA-protein cross-links in NB4 and HL60 cells were sensitive to modulators of calcium, NO synthase, oxidant, and myeloperoxidase. Therefore, although oxidized guanine products were detected in all the human cells treated with arsenite, the pathways could be different in different cell types. Because the sensitivity and the mechanism of arsenic intoxication are cell specific, it is important that target tissues and target cells are used for investigations. It is also important that pathologically or pharmacologically meaningful concentrations of arsenic are used. This is because in most cases we are dealing with the chronic effect rather than acute toxicity.
引用
收藏
页码:753 / 756
页数:4
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