Rahman Q, Mahmood N, Khan S G, Arif J M, Athar M
Industrial Toxicology Research Centre, Lucknow, India.
Environ Health Perspect. 1997 Sep;105 Suppl 5(Suppl 5):1109-12. doi: 10.1289/ehp.97105s51109.
Several observations, including studies from this laboratory, demonstrate that asbestos generates free radicals in the biological system that may play a role in the manifestation of asbestos-related cytotoxicity and carcinogenicity. It has also been demonstrated that iron associated with asbestos plays an important role in the asbestos-mediated generation of reactive oxygen species. Exposure to asbestos leads to degradation of heme proteins such as cytochrome P450-releasing heme in cytosol. Our simulation experiments in the presence of heme show that such asbestos-released heme may increase lipid peroxidation and can cause DNA damage. Further, heme and horseradish peroxidase (HRP) can cause extensive DNA damage in the presence of asbestos and hydrogen peroxide/organic peroxide/hydroperoxides. HRP catalyzes oxidation reactions in a manner similar to that of prostaglandin H synthetase. Iron released from asbestos is only partially responsible for DNA damage. However, our studies indicate that DNA damage mediated by asbestos in vivo may be caused by a combination of effects such as the release and participation of iron, heme, and heme moiety of prostaglandin H synthetase in free radical generation from peroxides and hydroperoxides.
包括本实验室研究在内的多项观察结果表明，石棉在生物系统中会产生自由基，这些自由基可能在石棉相关的细胞毒性和致癌性表现中发挥作用。研究还表明，与石棉结合的铁在石棉介导的活性氧生成中起重要作用。接触石棉会导致细胞色素P450等血红素蛋白降解，从而在细胞质中释放血红素。我们在血红素存在下进行的模拟实验表明，这种石棉释放的血红素可能会增加脂质过氧化，并可能导致DNA损伤。此外，在石棉和过氧化氢/有机过氧化物/氢过氧化物存在的情况下，血红素和辣根过氧化物酶（HRP）会导致广泛的DNA损伤。HRP催化氧化反应的方式与前列腺素H合成酶类似。从石棉中释放的铁只是导致DNA损伤的部分原因。然而，我们的研究表明，石棉在体内介导的DNA损伤可能是由多种效应共同作用引起的，例如铁、血红素以及前列腺素H合成酶的血红素部分从过氧化物和氢过氧化物中生成自由基时的释放和参与。
