致癌性卤代醌类消毒副产物造成 DNA 损伤的分子机理研究  

Mechanism Investigation on DNA Damage Induced by Carcinogenic Haloquinoid Disinfection Byproducts

作　　者：朱本占[1,2] 张静 唐苗[1,2] 黄春华 邵杰 Benzhan Zhu;Jing Zhang;Miao Tang;Chunhua Huang;Jie Shao(State Key Laboratory of Environmental Chemistry and Ecotoxicology,Research Center for Eco-Environmental Sciences,Chinese Academy of Sciences,Beijing 100085,China;University of Chinese Academy of Sciences,Beijing 100049,China)

机构地区：[1]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,北京100085 [2]中国科学院大学,北京100049

出　　处：《化学进展》2022年第1期227-236,共10页Progress in Chemistry

基　　金：中国科学院战略性先导科技专项项目(No.XDB14030100);中国科学院基础前沿科学研究计划从“0”到“1”原始创新项目(No.ZDBS-LYSLH027);国家自然科学基金项目(No.21976200、21207150、21836005、21621064、21321004);中科院生态环境研究中心青年科学家基金(No.RCEES-QN-20130052F)资助。

摘　　要：卤代醌是一类卤代芳烃类环境污染物的致癌中间体,也是在饮用水中新发现的氯化消毒副产物。我们最近发现卤代醌和H_(2)O_(2)或有机氢过氧化物体系可以不依赖过渡金属离子,而产生高活性的羟基/烷氧自由基和醌氧/醌碳自由基。目前尚不清楚这些卤代醌类致癌物和氢过氧化物共存能否诱导DNA产生氧化损伤和修饰,以及其潜在的分子机制是什么。我们的研究发现DNA在四氯-1,4-苯醌/H_(2)O_(2)体系中可被氧化产生8-氧脱氧鸟苷、DNA链断裂和三种甲基氧化产物,这些反应不依赖过渡金属离子,且由于卤代醌与DNA的嵌入作用而导致其氧化作用增强。其他卤代醌也观察到了类似的现象,而且通常比经典的Fenton体系更有效。我们进一步将研究从纯化的DNA扩展到了活细胞的基因组DNA。同时还发现卤代醌和有机氢过氧化物(如叔丁基过氧化氢或在正常生理条件下产生的13S-过氧羟基-9Z,11E-十八碳二烯酸(13-HPODE))共存时,可通过独特的醌氧自由基介导机制诱导DNA氧化生成致突变性更强的咪唑啉酮类产物dIz。这些发现为解释普遍存在的卤代醌类致癌中间体和消毒副产物的潜在基因毒性、致突变性和致癌性提供了新思路。Halobenzoquinones(HBQs) are a class of toxic intermediates of the haloaromatic persistent organic pollutants and newly identified chlorination disinfection byproducts in drinking water and swimming pool water. The highly reactive hydroxyl/alkoxyl radicals and quinone enoxy/ketoxy radicals were found to be produced by HBQs with H_(2)O_(2)or organic hydroperoxides metal-independently. However, it remains unknown whether HBQs and hydroperoxides can induce DNA damage, and if so, what are the underlying molecular mechanisms. We found that 8-oxodeoxyguanosine(8-oxodG), DNA strand breaks and three methyl oxidation products could be generated from DNA oxidation by tetrachloro-1,4-benzoquinone(TCBQ) and H_(2)O_(2)via an intercalation-enhanced oxidation mechanism. Analogous effects were observed with other HBQs, which are generally more effective than the classic iron-mediated Fenton system. Further investigations were extended from isolated DNA to genomic DNA in living cells. Potent oxidation of DNA to the more mutagenic imidazolone dIz was also found to be induced by HBQs and organic hydroperoxides such as the physiologically-relevant hydroperoxide 13S-hydroperoxy-9Z,11E-octadecadienoic acid(13-HPODE) via a unique quinone-enoxy radical-mediated mechanism. These findings should provide new perspectives to explain the potential genotoxicity, mutagenesis, and carcinogenicity for the ubiquitously-present haloaromatic persistent organic pollutants.

关 键 词：卤代醌 氢过氧化物 自由基 DNA损伤 基因毒性 

分 类 号：X5[环境科学与工程—环境工程] O69[理学—化学]