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 resul ted in the formation of 8-hydroxy-2'deoxyguanosine (8-OHdG) in the DNA , synthesis of mRNA for the inducible form of nitric oxide synthase (N OS), and increased intracellular nitrite (NO2-), a stable oxidation pr oduct of NO. Iron, associated with crocidolite, was involved in both N O2- and 8-OHdG formation. Addition of the NOS inhibitor, aminoguanidin e (AG), reduced intracellular NO2- and prevented formation of 8-OHdG i n 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 suppo rting a role for NO in oxidation of deoxyguanosine. (C) 1996 Academic Press, Inc.