Faux S P, Howden P J, Levy L S
Institute of Occupational Health, University of Birmingham, Edgbaston, UK.
Carcinogenesis. 1994 Aug;15(8):1749-51. doi: 10.1093/carcin/15.8.1749.
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.
用青石棉处理分离出的DNA，可使8-羟基脱氧鸟苷（8-OHdG）的浓度显著高于本底水平。此外，将DNA与过氧化氢和青石棉一起孵育，可使8-OHdG的形成比单独使用青石棉时观察到的水平更高。在去铁胺、去铁胺与亚铁嗪、二甲基亚砜（DMSO）或邻菲罗啉存在的情况下，青石棉诱导的DNA氧化分别降低了36%、73%、74%和70%。在鼠伤寒沙门氏菌TA102中，亚细胞毒性浓度的青石棉（而非温石棉）以剂量依赖的方式增强了本底回复突变率。青石棉的诱变作用相当小，这表明在本研究中，青石棉是一种弱诱变剂。在用该对氧自由基敏感的菌株检测遗传毒性之前，先用去铁胺预处理纤维后，回复突变体的数量降至该菌株的自发率。这些结果有助于解释铁在青石棉诱导的TA102 DNA氧化和诱变中的作用机制。
