| Mechanistic Study on Oxidative DNA Damage and Modifications by Haloquinoid Carcinogenic Intermediates and Disinfection Byproducts | |
Zhu, Ben-Zhan; Tang, Miao; Huang, Chun-Hua ; Mao, Li; Shao, Jie
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| 2021-07-19 | |
| Source Publication | CHEMICAL RESEARCH IN TOXICOLOGY
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| ISSN | 0893-228X |
| Volume | 34Issue:7Pages:1701-1712 |
| Abstract | Haloquinones (XQs) are a group of carcinogenic intermediates of the haloaromatic environmental pollutants and newly identified chlorination disinfection byproducts (DBPs) in drinking water. The highly reactive hydroxyl radicals/alkoxyl radicals and quinone enoxy/ketoxy radicals were found to arise in XQs and H2O2 or organic hydroperoxides system, independent of transition-metal ions. However, it was not clear whether these haloquinoid carcinogens and hydroperoxides can cause oxidative DNA damage and modifications, 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 arise when DNA was treated with tetrachloro-1,4-benzoquinone and H2O2 via a metal-independent and intercalation-enhanced oxidation mechanism. Similar effects were observed with other XQs, which are generally more efficient than the typical Fenton system. We further extended our studies from isolated DNA to genomic DNA in living cells. We also found that potent oxidation of DNA to the more mutagenic imidazolone dIz could be induced by XQs and organic hydroperoxides such as t-butylhydroperoxide or the physiologically relevant hydroperoxide 13S-hydroperoxy-9Z,11E-octadecadienoic acid via an unprecedented quinone-enoxy radical-mediated mechanism. These findings should provide new perspectives to explain the potential genotoxicity, mutagenesis, and carcinogenicity for the ubiquitous haloquinoid carcinogenic intermediates and DBPs. |
| Department | 环境化学与生态毒理学国家重点实验室 |
| WOS Research Area | Chemistry, Medicinal ; Chemistry, Multidisciplinary ; Toxicology |
| Document Type | 期刊论文 |
| Identifier | https://ir.rcees.ac.cn/handle/311016/45773 |
| Collection | 环境化学与生态毒理学国家重点实验室 |
| Affiliation | 1.Chinese Acad Sci, Res Ctr Ecoenvironm Sci, State Key Lab Environm Chem & Ecotoxicol, Beijing 100085, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China |
| Recommended Citation GB/T 7714 | Zhu, Ben-Zhan,Tang, Miao,Huang, Chun-Hua,et al. Mechanistic Study on Oxidative DNA Damage and Modifications by Haloquinoid Carcinogenic Intermediates and Disinfection Byproducts[J]. CHEMICAL RESEARCH IN TOXICOLOGY,2021,34(7):1701-1712. |
| APA | Zhu, Ben-Zhan,Tang, Miao,Huang, Chun-Hua,Mao, Li,&Shao, Jie.(2021).Mechanistic Study on Oxidative DNA Damage and Modifications by Haloquinoid Carcinogenic Intermediates and Disinfection Byproducts.CHEMICAL RESEARCH IN TOXICOLOGY,34(7),1701-1712. |
| MLA | Zhu, Ben-Zhan,et al."Mechanistic Study on Oxidative DNA Damage and Modifications by Haloquinoid Carcinogenic Intermediates and Disinfection Byproducts".CHEMICAL RESEARCH IN TOXICOLOGY 34.7(2021):1701-1712. |
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