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过氧化氢和有机过氧化物在增强石棉介导的DNA损伤中的不同作用:对石棉诱导致癌作用的影响

Differential role of hydrogen peroxide and organic peroxides in augmenting asbestos-mediated DNA damage: implications for asbestos induced carcinogenesis.

作者信息

Mahmood N, Khan S G, Athar M, Rahman Q

机构信息

Fiber Toxicology Section, Industrial Toxicology Research Centre, Lucknow, India.

出版信息

Biochem Biophys Res Commun. 1994 Apr 29;200(2):687-94. doi: 10.1006/bbrc.1994.1505.

DOI:10.1006/bbrc.1994.1505
PMID:8179601
Abstract

The incubation of asbestos with DNA in presence of peroxides augmented DNA damage several fold as compared to the damage caused by individual treatments. Asbestos in presence of hydrogen peroxide causes DNA double strand breaks, damage to its deoxyribose sugar moiety and enhanced DNA fidelity. However, only DNA double strand breaks and enhanced DNA fidelity could be recorded in presence of organic hydroperoxide/peroxide but no DNA sugar damage could be observed. Further, the extent of DNA damage could be correlated to the carcinogenic potential of asbestos fibre. Crocidolite, the most carcinogenic variety of asbestos, produces maximum damage to DNA in presence of both hydrogen peroxide and organic hydroperoxide/peroxide while chrysolite which is only a co-carcinogen produces significantly less DNA damage. The observed differences in DNA damage by hydrogen peroxide and organic hydroperoxide/peroxide have been ascribed to the differential reactivity of DNA with hydroxyl and alkoxy/aryloxy free radicals produced respectively from these inorganic and organic peroxides.

摘要

与单独处理所造成的损伤相比,在过氧化物存在的情况下,石棉与DNA一起温育会使DNA损伤增加数倍。在过氧化氢存在的情况下,石棉会导致DNA双链断裂、其脱氧核糖糖部分受损以及DNA保真度提高。然而,在有机氢过氧化物/过氧化物存在的情况下,只能记录到DNA双链断裂和DNA保真度提高,而未观察到DNA糖损伤。此外,DNA损伤的程度可能与石棉纤维的致癌潜力相关。青石棉是最具致癌性的石棉品种,在过氧化氢和有机氢过氧化物/过氧化物同时存在的情况下,对DNA造成的损伤最大,而仅作为促癌剂的温石棉造成的DNA损伤则明显较少。过氧化氢和有机氢过氧化物/过氧化物对DNA损伤的观察到的差异归因于DNA分别与由这些无机和有机过氧化物产生的羟基和烷氧基/芳氧基自由基的不同反应性。

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Mechanism of asbestos-mediated DNA damage: role of heme and heme proteins.石棉介导的DNA损伤机制:血红素和血红素蛋白的作用。
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Mechanisms of fiber-induced genotoxicity.纤维诱导的遗传毒性机制。
Environ Health Perspect. 1997 Sep;105 Suppl 5(Suppl 5):1073-84. doi: 10.1289/ehp.97105s51073.