Participation of nitric oxide and iron in the oxidation of DNA in asbestos-treated human lung epithelial cells.
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.
Chao
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Department of Chemistry and Biochemistry, Utah State University, Logan 84322-0300, USA.
Park
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Aust
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D001194:Asbestos / Q000633:toxicity*; D001483:Base Sequence; D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line; D004247:DNA / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000378:metabolism*; D010084:Oxidation-Reduction
D002273:Carcinogens; D001194:Asbestos; D009569:Nitric Oxide; D004247:DNA; D007501:Iron