多环芳胺致癌的新型自由基机制:光致羟基自由基的生成及DNA损伤
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- 英文论文题名：A novel radical mechanism for carcinogenicity of polycyclic aromatic amines:photo-induced hydroxyl radical formation and DNA damage
- 论文作者：徐丹 ; 朱本占
- 英文论文作者：Dan Xu ; Ben-Zhan Zhu ; Research Center 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;
- 论文关键词：多环芳胺 ; N-羟基-乙酰基氨基芴 ; 光照 ; 羟基自由基 ; DNA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：R730.2
- 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：208k
- 原文格式：D
- 会议级别：全国
摘要
羟基自由基(·OH)被公认是生物系统中产生的最具活性的活性氧物种,能导致生物体内DNA,蛋白质和脂质氧化损伤。过渡金属离子催化的Fenton反应是·OH产生的经典机制。N-羟基-乙酰基氨基芴(N-OH-AAF)是环境污染物多环芳胺2-硝基芴的主要致癌代谢产物。先前文献报道N-OH-AAF主要通过体内酶活化为氮正离子途径形成致癌性DNA加合物[1]。最近我们意外发现光照N-OH-AAF不仅可导致DNA的单双链断裂,还可生成DNA氧化损伤的生物标志物8-OHd G和几种不同的DNA加合物,而·OH猝灭剂可抑制DNA单双链断裂和8-OHd G的生成。ESR自旋捕获研究发现光照N-OH-AAF可产生·OH及其他活性自由基。综上,我们发现N-OH-AAF在光照条件下可产生·OH,其可导致DNA氧化损伤和单双链断裂。本研究提出了一种光诱导N-OH-AAF均裂分解产生·OH的新机制,这可能是一种潜在的N-OH-AAF的活化途径,为理解多环芳胺的致癌分子机制提供了崭新的研究视角。
Hydroxyl radicals(·OH) can cause DNA,protein,and lipid oxidation.The classical method to generate ·OH is through Fenton reaction.N-hydroxy-acetyl-2-aminofluorene(N-OH-AAF) is a major carcinogenic metabolite of 2-nitroflurene.The carcinogenicity of N-OH-AAF has been mainly attributed to the formation of DNA adducts via nitrium ion intermediate by enzymatic activation.Recently,we found,unexpectedly,that photolysis of N-OH-AAF can induce the formation of not only DNA strand breaks,but also 8-OHd G and DNA adducts.ESR spin-trapping studies confirmed that ·OH and other radical intermdiates were generated by photolysis of N-OH-AAF.We concluded that ·OH can be generated by photolysis of N-OH-AAF,which are responsible for oxidative DNA damages.This study proposed a new mechanism for ·OH formation by photolysis of N-OH-AAF.As a new potential pathway for N-OH-AAF activation,this study provides a new perspective to understand the molecular mechanism for the carcinogenicity of polycyclic aromatic amines.
Hydroxyl radicals(·OH) can cause DNA,protein,and lipid oxidation.The classical method to generate ·OH is through Fenton reaction.N-hydroxy-acetyl-2-aminofluorene(N-OH-AAF) is a major carcinogenic metabolite of 2-nitroflurene.The carcinogenicity of N-OH-AAF has been mainly attributed to the formation of DNA adducts via nitrium ion intermediate by enzymatic activation.Recently,we found,unexpectedly,that photolysis of N-OH-AAF can induce the formation of not only DNA strand breaks,but also 8-OHd G and DNA adducts.ESR spin-trapping studies confirmed that ·OH and other radical intermdiates were generated by photolysis of N-OH-AAF.We concluded that ·OH can be generated by photolysis of N-OH-AAF,which are responsible for oxidative DNA damages.This study proposed a new mechanism for ·OH formation by photolysis of N-OH-AAF.As a new potential pathway for N-OH-AAF activation,this study provides a new perspective to understand the molecular mechanism for the carcinogenicity of polycyclic aromatic amines.
引文
[1]De Baun,J.R.,et al.Science.1970,167:184-186.