Mahmood N, Khan S G, Ali S, Athar M, Rahman Q
Industrial Toxicology Research Centre, Lucknow, India.
Ann Occup Hyg. 1993 Jun;37(3):315-9. doi: 10.1093/annhyg/37.3.315.
DNA-damaging effects of asbestos in the presence of organic peroxides and hydroperoxides were investigated. The destabilization of the secondary structure of DNA, damage to deoxyribose sugar and DNA fidelity were measured, respectively, by S-1 nuclease hydrolysis, the formation of thiobarbituric acid (TBA)-reacting species and a melting temperature (Tm) profile using calf thymus DNA. S-1 nuclease hydrolysis and Tm determinations have shown that the presence of benzoylperoxide (BOOB), cumene hydroperoxide (COOH) or tertiary-butyl hydroperoxide (t-BOOH) increased asbestos-mediated DNA damage by a large factor compared either to asbestos alone or to peroxide or hydroperoxide alone. However, no formation of TBA-reacting species could be observed in this system. The quenchers of reactive oxygen species (ROS) afforded protection against DNA damage. These results suggest that asbestos in the presence of organic peroxides and hydroperoxides damage the DNA which is mediated by the generation of oxygen free radicals. The significance of these results in relation to the development of cancer of the respiratory tract among the asbestos exposed population is discussed.
研究了在有机过氧化物和氢过氧化物存在下石棉对DNA的损伤作用。分别使用小牛胸腺DNA，通过S-1核酸酶水解、硫代巴比妥酸（TBA）反应产物的形成以及解链温度（Tm）曲线，来测定DNA二级结构的不稳定、脱氧核糖损伤和DNA保真度。S-1核酸酶水解和Tm测定表明，与单独的石棉或单独的过氧化物或氢过氧化物相比，过氧化苯甲酰（BOOB）、异丙苯过氧化氢（COOH）或叔丁基过氧化氢（t-BOOH）的存在会大幅增加石棉介导的DNA损伤。然而，在该系统中未观察到TBA反应产物的形成。活性氧（ROS）淬灭剂可提供对DNA损伤的保护。这些结果表明，在有机过氧化物和氢过氧化物存在下，石棉会损伤DNA，这是由氧自由基的产生介导的。讨论了这些结果与石棉暴露人群呼吸道癌症发生的相关性。
