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环境化学  2015 

致突变的致癌剂和非致癌剂在引发DNA股间交联上的显著差别

Keywords: 致癌机理,双区理论,DNA股间横向交联,溴代烷烃,,羟胺,APCI/SIM质谱

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Abstract:

借碱洗脱法证明具有致突变能力的致癌剂1,2-二溴乙烷和肼在经过代谢活化后,均剂量相关地引起L1210细胞中DNA的股间交联。相反,动物致癌试验表现阴性的致突变剂溴乙烷,以及通过各种致癌动物试验均显示阴性的传统常用致突变剂羟胺,在代谢活化以后的同样条件下均不能引起L1210细胞中DNA的股间交联。这证明了双区理论的致癌机理观点,即致癌剂必须是双官能烷化剂,其同时引起互补碱对的交联将引起癌变。相反,股内单一碱基的变异则可能引起致突变作用。并用APCI/SIM(大气压化学电离/选择离子质谱)证明1,2-二溴乙烷与DNA碱基对的模型反应,与致突实验一致主要引起G-C对的交联和发生G-C→A-T突变。

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