Franzén R, Goto S, Tanabe K, Morita M
University of Helsinki, Department of Pharmacy, P.O. Box 56, FIN-00014, Helsinki, Finland.
Mutat Res. 1998 Sep 1;417(1):31-7. doi: 10.1016/s1383-5718(98)00092-8.
The mutagenic activities of several chlorinated butenoic acids, recently identified in chlorinated drinking waters, were determined by the Salmonella microsome assay. The Salmonella typhimurium tester strains TA98, TA100, and TA104 were used without S9 mix. The results from the investigation showed that (Z)-2-chloro-3-(dichloromethyl)-4-oxobutenoic acid (MX, in the open form) was the most potent mutagen of the compounds tested. However, a significant number of mutations was also induced by compounds with structural similarities to MX. In general, all the compounds, except the butenedioic acids, were mutagenic in the assays for both base-pair substitution strains (TA100, TA104) and for the frameshift strain TA98, with the highest mutagenic response observed in strain TA100. When the aldehyde group of MX and of 2-chloro-3-(chloromethyl)-4-oxobutenoic acid (CMCF, in the open form) was replaced by a dichloromethyl group, the mutagenic response in strains TA98 and TA104 changed. We concluded that a frame-shift mutation occurred because of the replacement. The increase of the TA104 mutagenicity suggested that adenosine could be the target for these types of compounds. Further evidence for such possibility were the modified adenosine adducts we could identify for some chlorinated butenoic acids.
通过沙门氏菌微粒体试验测定了最近在氯化饮用水中发现的几种氯化丁烯酸的致突变活性。使用鼠伤寒沙门氏菌测试菌株TA98、TA100和TA104，不添加S9混合物。调查结果表明，（Z）-2-氯-3-（二氯甲基）-4-氧代丁烯酸（MX，开环形式）是所测试化合物中最有效的诱变剂。然而，与MX结构相似的化合物也诱导了大量突变。一般来说，除丁烯二酸外，所有化合物在碱基对取代菌株（TA100、TA104）和移码菌株TA98的试验中都具有致突变性，在TA100菌株中观察到最高的诱变反应。当MX和2-氯-3-（氯甲基）-4-氧代丁烯酸（CMCF，开环形式）的醛基被二氯甲基取代时，TA98和TA104菌株中的诱变反应发生了变化。我们得出结论，这种取代导致了移码突变。TA104诱变活性的增加表明腺苷可能是这些类型化合物的作用靶点。我们能够鉴定出一些氯化丁烯酸的修饰腺苷加合物，这进一步证明了这种可能性。
