Mechanism of unprecedented hydroxyl radical production and site-specific oxidative DNA damage by photoactivation of the classic arylhydroxamic acid carcinogens
文献类型：期刊论文
| 作者 | Xu, Dan; Huang, Chun-Hua; Xie, Lin-Na; Shao, Bo; Mao, Li; Shao, Jie; Kalyanaraman, Balaraman2; Zhu, Ben-Zhan |
| 刊名 | CARCINOGENESIS
 |
| 出版日期 | 2019-09-01 |
| 卷号 | 40期号:9页码:1153-1163 |
| ISSN号 | 0143-3334 |
| 英文摘要 | The carcinogenicity of N-hydroxy-2-acetamidofluorene (N-OHAAF), the major genotoxic metabolite of the classic model aromatic amine (AA) carcinogen 2-acetylaminofluorene, has been attributed mainly to the formation of DNA adducts via arylnitrenium upon enzymatic activation. Here, we show, unexpectedly, that exposure of N-OHAAF to UV or sunlight irradiation can not only induce the formation of the well-known covalent DNA adducts, but, more interestingly, simultaneous generation of oxidative DNA damage was also observed as measured by the formation of DNA single-/ double-strand breaks (SSBs/DSBs) and 8-oxo-2'-deoxyguanosine (8-oxodG), which were partly inhibited by the typical hydroxyl radical ((OH)-O-center dot) scavengers. Electron spin resonance spin-trapping and fluorescent studies unequivocally confirmed that the highly reactive (OH)-O-center dot was generated from photolysis of N-OHAAF. Further DNA sequencing investigations suggest that photoactivation of N-OHAAF caused preferential cleavage at guanine, thymine and cytosine sites. More importantly, the formation of 8-oxodG and DSBs were also observed when fibroblast Balb/c-3T3 cells were co-exposed to N-OHAAF/UV irradiation as measured by double immunofluorescence staining. Taken together, we propose that both (OH)-O-center dot and amidyl radicals can be readily produced via N-OH homolysis in N-OHAAF by photoirradiation, which can induce both oxidative and covalent DNA damage. This represents the first report of (OH)-O-center dot production and site-specific DNA damage via photoactivation of the genotoxic hydroxamic acid intermediate, which provides a new free radical perspective to better understand the molecular mechanism for the carcinogenicity of AAs. |
| 源URL | [http://ir.rcees.ac.cn/handle/311016/42561]  |
| 专题 | 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 |
| 作者单位 | 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 3.Med Coll Wisconsin, Dept Biophys, Milwaukee, WI 53226 USA 4.Oregon State Univ, Linus Pauling Inst, Corvallis, OR 97331 USA |
| 推荐引用方式 GB/T 7714 | Xu, Dan,Huang, Chun-Hua,Xie, Lin-Na,et al. Mechanism of unprecedented hydroxyl radical production and site-specific oxidative DNA damage by photoactivation of the classic arylhydroxamic acid carcinogens[J]. CARCINOGENESIS,2019,40(9):1153-1163. |
| APA | Xu, Dan.,Huang, Chun-Hua.,Xie, Lin-Na.,Shao, Bo.,Mao, Li.,...&Zhu, Ben-Zhan.(2019).Mechanism of unprecedented hydroxyl radical production and site-specific oxidative DNA damage by photoactivation of the classic arylhydroxamic acid carcinogens.CARCINOGENESIS,40(9),1153-1163. |
| MLA | Xu, Dan,et al."Mechanism of unprecedented hydroxyl radical production and site-specific oxidative DNA damage by photoactivation of the classic arylhydroxamic acid carcinogens".CARCINOGENESIS 40.9(2019):1153-1163. |
入库方式： OAI收割
来源：生态环境研究中心
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。