致癌性卤代醌介导的新型自由基反应诱导DNA氧化损伤的机理研究
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- 英文论文题名：Novel Mechanism of DNA Oxidation Induced by Carcinogenic Halogenated Quinones and Hydroperoxides
- 论文作者：邵杰 ; 朱本占
- 英文论文作者：Jie Shao ; Ben-Zhan Zhu ; State Key Laboratory of Environmental Chemistry and Ecotoxicology ; Research Centre for Eco-Environmental Sciences ; Chinese Academy of Sciences
- 年：2016
- 作者机构：中国科学院生态环境研究中心环境化学与生态毒理学国家重点实验室;
- 论文关键词：卤代醌 ; 氢过氧化物 ; DNA氧化损伤
- 会议召开时间：2016-07-01
- 会议录名称：中国化学会第30届学术年会摘要集-第二十六分会：环境化学
- 语种：中文
- 分类号：X171.5;O643.12
- 学会代码：ZGHY
- 会议名称：中国化学会第30届学术年会-第二十六分会 ; 环境化学
- 会议地点：中国辽宁大连
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：1
- 文件大小：179k
- 原文格式：D
- 会议级别：全国
摘要
卤代醌作为环境中广泛存在的一类污染物,其毒性机理逐渐受到人们关注,研究显示卤代醌类化合物对生物体具有多种毒性作用,如免疫毒性、细胞毒性和基因毒性等。四氯-1,4-苯醌(TCBQ)是木材保护剂五氯酚的主要代谢产物。TCBQ和氢过氧化物反应可以产生一系列活泼自由基包括烷氧自由基、烷基、碳醌自由基。但是不清楚这种卤代醌介导的新型自由基反应能否对鸟嘌呤造成氧化损伤;如果可以,可能的反应机理如何。经过实验我们发现TCBQ和t-Bu OOH不仅把2’-脱氧鸟苷d G氧化成8oxod G还有新的氧化产物2,5-diamino-4H-imidazolone(d Iz)生成。这两种氧化产物可以被典型自由基捕获剂显著抑制,而且排除了羟基自由基和超氧自由基的作用。通过与其它卤代醌体系以及金属离子诱导体系相比,我们推测TCBQ和t-Bu OOH反应生成的醌氧自由基可能在Iz的生成中起到重要作用。通过18O2实验证实d Iz上的O来自O2。在实验基础上我们提出了鸟嘌呤被TCBQ/t-Bu OOH氧化可能的反应机理:TCBQ和t-Bu OOH反应生成的醌氧自由基可能夺取鸟嘌呤上的氢生成相应的自由基,与氧气结合后经过重排后生成Iz。本研究部分解释了广泛使用的多卤芳香化合物的潜在致癌性。
Tetrachloro-1,4-benzoquinone(TCBQ) is one of the major genotoxic metabolites of wood preservative pentachlorophenol.TCBQ and t-Bu OOH can produce highly reactive free radicals independent of transition metal ions including alkoxyl,alkyl,quinone ketoxy and enoxy radical.Recently we found that 2'-deoxyguanosine(d G) could be oxidized to 8oxod G and 2,5-diamino-4H-imidazolone(d Iz) by TCBQ and t-Bu OOH.The formation of the two oxidation products was markedly inhibited by typical free radicals trapping agents.Compared with other halogenated quinones and the Fe(II) mediated system,we found that the oxygen-centered quinone enoxy radical might play an important role in the formation of d Iz.The 18O2 experiment indicated the oxygen of d Iz originate from O2.Based on these data,we proposed that the oxidation of d G by TCBQ/t-Bu OOH might be through the following mechanism:the oxygen-centered quinone enoxy radical produced by TCBQ/t-Bu OOH may abstract hydrogen from d G,leading to the formation of corresponding radical,which may combine with O2.Iz can be produced through subsequent rearrangement reactions.This study may partly explain the potential carcinogenicity of the widely used halogenated aromatic compounds.
Tetrachloro-1,4-benzoquinone(TCBQ) is one of the major genotoxic metabolites of wood preservative pentachlorophenol.TCBQ and t-Bu OOH can produce highly reactive free radicals independent of transition metal ions including alkoxyl,alkyl,quinone ketoxy and enoxy radical.Recently we found that 2'-deoxyguanosine(d G) could be oxidized to 8oxod G and 2,5-diamino-4H-imidazolone(d Iz) by TCBQ and t-Bu OOH.The formation of the two oxidation products was markedly inhibited by typical free radicals trapping agents.Compared with other halogenated quinones and the Fe(II) mediated system,we found that the oxygen-centered quinone enoxy radical might play an important role in the formation of d Iz.The 18O2 experiment indicated the oxygen of d Iz originate from O2.Based on these data,we proposed that the oxidation of d G by TCBQ/t-Bu OOH might be through the following mechanism:the oxygen-centered quinone enoxy radical produced by TCBQ/t-Bu OOH may abstract hydrogen from d G,leading to the formation of corresponding radical,which may combine with O2.Iz can be produced through subsequent rearrangement reactions.This study may partly explain the potential carcinogenicity of the widely used halogenated aromatic compounds.
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