Mechanism of site-specific DNA damage induced by ozone
Mechanism of site-specific DNA damage induced by ozone
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DOI：
10.1016/j.mrgentox.2005.04.004
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发表时间：
2005-08-01
影响因子：
1.9
通讯作者：
Kawanishi, S
中科院分区：
文献类型：
--
作者：
Ito, K;Inoue, S;Kawanishi, S
臭氧已被证明会诱发小鼠肺肿瘤。用32 P标记的DNA片段进行DNA测序，研究了臭氧与水溶液中DNA的反应性。臭氧诱导的双链DNA的脱氧核糖磷酸骨架的裂解，这是减少的羟基自由基清除剂，表明在裂解的羟基自由基的参与。臭氧诱导的DNA裂解增强与哌啶处理，诱导裂解的碱基修饰的网站，但羟基自由基清除剂对哌啶诱导的裂解的抑制作用是有限的。主要哌啶不稳定位点是鸟嘌呤和胸腺嘧啶残基。裂解在一些鸟嘌呤和胸腺嘧啶残基哌啶治疗后变得更加突出与变性的单链DNA。小牛胸腺DNA暴露于臭氧导致8-氧代-7，8-二氢-2 '-脱氧鸟苷形成的剂量依赖性增加，这部分被羟基自由基清除剂抑制。使用5，5-二甲基吡咯啉-N-氧化物（DMPO）的ESR研究表明，含水臭氧产生的DMPO的羟基自由基加合物。此外，在缓冲溶液中，臭氧分解过程中检测到荧光素依赖的化学发光，并观察到D2 O的增强效应，表明单线态氧的形成。而D_2O对臭氧诱导的DNA损伤没有或几乎没有增强作用。这些结果表明，臭氧通过产生羟基自由基引起DNA骨架断裂，而DNA碱基修饰主要由臭氧本身引起，羟基自由基和/或单线态氧在碱基修饰中的参与很小。臭氧引起的DNA损伤炎症相关的致癌作用以及空气污染相关的致癌作用的可能联系进行了讨论。(c)2005 Elsevier B. V.保留所有权利。
Ozone has been shown to induce lung tumors in mice. The reactivity of ozone with DNA in an aqueous solution was investigated by a DNA sequencing technique using 32 P-labeled DNA fragments. Ozone induced cleavages in the deoxyribose-phosphate backbone of double-stranded DNA, which were reduced by hydroxyl radical scavengers, suggesting the participation of hydroxyl radicals in the cleavages. The ozone-induced DNA cleavages were enhanced with piperidine treatment, which induces cleavages at sites of base modification, but the inhibitory effect of hydroxyl radical scavengers on the piperidine-induced cleavages was limited. Main piperidine-labile sites were guanine and thymine residues. Cleavages at some guanine and thymine residues after piperidine treatment became more predominant with denatured single-stranded DNA. Exposure of calf thymus DNA to ozone resulted in a dose-dependent increase of the 8-oxo-7,8-dihydro-2'-deoxyguanosine formation, which was partially inhibited by hydroxyl radical scavengers. ESR studies using 5,5-dimethylpyrroline-N-oxide (DMPO) showed that aqueous ozone produced the hydroxyl radical adduct of DMPO. In addition, the fluorescein-dependent chemiluminescence was detected during the decomposition of ozone in a buffer solution and the enhancing effect of D2O was observed, suggesting the formation of singlet oxygen. However, no or little enhancing effect of D2O on the ozone-induced DNA damage was observed. These results suggest that DNA backbone cleavages were caused by ozone via the production of hydroxyl radicals, while DNA base modifications were mainly caused by ozone itself and the participation of hydroxyl radicals and/or singlet oxygen in base modifications is small, if any. A possible link of ozone-induced DNA damage to inflammation-associated carcinogenesis as well as air pollution-related carcinogenesis is discussed. (c) 2005 Elsevier B.V. All rights reserved.