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.