IRON-DEPENDENT FORMATION OF 8-HYDROXYDEOXYGUANOSINE IN ISOLATED DNA AND MUTAGENICITY IN SALMONELLA-TYPHIMURIUM TA102 INDUCED BY CROCIDOLITE

Treatment of isolated DNA with crocidolite asbestos significantly incr eased the concentration of 8-hydroxydeoxyguanosine (8-OHdG) above back ground. Furthermore, incubating DNA with H2O2 and crocidolite potentia ted the formation of 8-OHdG above levels observed with crocidolite alo ne. In the presence of desferrioxamine, desferrioxamine and ferrozine, dimethylsulphoxide (DMSO) or o-phenanthroline, crocidolite-induced DN A oxidation was reduced by 36, 73, 74 and 70% respectively. Crocidolit e, but not chrysotile asbestos, enhanced background revertants in Salm onella typhimurium TA102, at sub-cytotoxic concentrations in a dose-de pendent manner. The mutagenic effects of crocidolite were quite small and this indicates that crocidolite was a weak mutagen in this study. The number of revertants was reduced to the spontaneous rate for this strain after the fibres had been pretreated with desferrioxamine befor e assaying for genotoxicity in this oxygen radical-sensitive strain. T hese results help to explain a mechanistic role for iron in crocidolit e-induced DNA oxidation and mutagenicity in TA102.