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 increased the concentration of 8-hydroxydeoxyguanosine (8-OHdG) above background. Furthermore, incubating DNA with H2O2 and crocidolite potentiated the formation of 8-OHdG above levels observed with crocidolite alone. In the presence of desferrioxamine, desferrioxamine and ferrozine, dimethylsulphoxide (DMSO) or o-phenanthroline, crocidolite-induced DNA oxidation was reduced by 36, 73, 74 and 70% respectively. Crocidolite, but not chrysotile asbestos, enhanced background revertants in Salmonella typhimurium TA102, at sub-cytotoxic concentrations in a dose-dependent 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 before assaying for genotoxicity in this oxygen radical-sensitive strain. These results help to explain a mechanistic role for iron in crocidolite-induced DNA oxidation and mutagenicity in TA102.
Faux
S P
SP
Institute of Occupational Health, University of Birmingham, Edgbaston, UK.
Howden
P J
PJ
Levy
L S
LS
D000080242:8-Hydroxy-2'-Deoxyguanosine; D017638:Asbestos, Crocidolite / Q000633:toxicity*; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D007501:Iron / Q000502:physiology*; D009154:Mutation; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics
D017638:Asbestos, Crocidolite; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D007501:Iron; D003849:Deoxyguanosine; D003676:Deferoxamine