1-氯-3-丁烯-2-醇的细胞遗传毒性  

Genotoxicity of 1-chloro-2-hydroxy-3-butene in cells

作　　者：李玉峰 刘欣杰 张新宇[1] LI Yufeng;LIU Xinjie;ZHANG Xinyu(Institute of Environmental Pollution and Health,School of Environmental and Chemical Engineering,Shanghai University,Shanghai 200444,China)

机构地区：[1]上海大学环境与化学工程学院环境污染与健康研究所

出　　处：《上海大学学报（自然科学版）》2019年第4期558-565,共8页Journal of Shanghai University:Natural Science Edition

基　　金：国家自然科学基金资助项目(21077070,21377080)

摘　　要：1-氯-3-丁烯-2-醇(1-chloro-2-hydroxy-3-butene,CHB)是致癌性空气污染物1,3-丁二烯的关键代谢产物,具有遗传毒性.研究了CHB损伤DNA的可能途径,发现无氯原子的对应化合物3-丁烯-2-醇(3-buten-2-ol,BO)没有遗传毒性,说明氯甲基是毒性的关键结构因素.CHB溶液放置较长时间(>4 h)后毒性增强,表明CHB可以缓慢转化为其他毒性更强的化合物.P450酶和乙醇脱氢酶抑制剂对CHB毒性没有影响;CHB毒性随着处理细胞时间的增加而增强,但在处理了12 h时反而减小.这些结果说明CHB的遗传毒性可能主要源于与DNA的直接反应,而非向1-氯-3-丁烯-2-酮(1-chloro-3-buten-2-one,CBO)的生物转化.1-chloro-2-hydroxy-3-butene(CHB)is a potentially critical metabolite of 1,3-butadiene,a carcinogenic air pollutant.It is genotoxic.This work studies the possible pathways for CHB to cause DNA damage.It has been found that the chloromethyl group in CHB was a pivotal factor in the structure because 3-buten-2-ol(BO),an analog of CHB without chlorine,was non-genotoxic.Genotoxicity of the pre-incubated CHB solution increased after the CHB solution was pre-incubated for a long time(>4 h),indicating that CHB could slowly be converted to other compounds with higher genotoxicity.The use of inhibitors of P450 and alcohol dehydrogenase had no effect on genotoxicity of CHB.Genotoxicity of CHB increased over cell-treatment time,but decreased at 12 h.The results suggested that genotoxicity of CHB may mostly stem from its capability to react with DNA rather than biotransformation to 1-chloro-3-buten-2-one(CBO).

关 键 词：1-氯-3-丁烯-2-醇 1-氯-3-丁烯-2-酮 1 3-丁二烯 代谢产物 遗传毒性 

分 类 号：R994.6[医药卫生—毒理学]