【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.更多还原

【Abstract】 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).更多还原