Participation of nitric oxide and iron in the oxidation of DNA in asbestos-treated human lung epithelial cells

被引:100
作者
Chao, CC [1 ]
Park, SH [1 ]
Aust, AE [1 ]
机构
[1] UTAH STATE UNIV,DEPT CHEM & BIOCHEM,LOGAN,UT 84322
关键词
asbestos; nitric oxide synthase; reactive oxygen radicals; DNA damage; iron; crocidolite; A549; cells; human lung epithelial cells;
D O I
10.1006/abbi.1996.0059
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Treatment of human lung epithelial (A549) cells with crocidolite resulted in the formation of 8-hydroxy-2'deoxyguanosine (8-OHdG) in the DNA, synthesis of mRNA for the inducible form of nitric oxide synthase (NOS), and increased intracellular nitrite (NO2-), a stable oxidation product of NO. Iron, associated with crocidolite, was involved in both NO2- and 8-OHdG formation. Addition of the NOS inhibitor, aminoguanidine (AG), reduced intracellular NO2- and prevented formation of 8-OHdG in crocidolite-treated cells, suggesting that NO was required in 8-OHdG formation. Addition of an NO-generating compound, diethyltriamine/NO, with AG and crocidolite resulted in recovery of 8-OHdG, further supporting a role for NO in oxidation of deoxyguanosine. (C) 1996 Academic Press, Inc.
引用
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页码:152 / 157
页数:6
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