Voutsinas G, Kappas A, Demopoulos N A, Catsoulacos P
Institute of Biology, National Research Center Democritus, Athens, Greece.
Mutat Res. 1993 Feb;298(4):261-7. doi: 10.1016/0165-1218(93)90005-x.
The ortho, meta and para isomers of N,N-bis(2-chloroethyl)aminocinnamic acid were tested for their ability to mutate Salmonella typhimurium strains in the Salmonella/microsome mutagenicity test. The aim of the work was to establish a structure-activity relationship between these three isomers. The drugs were found to induce base-pair substitutions, causing dose-dependent increases in his+ revertants, in strains TA100 and TA1535. The study showed that the position of the substituent groups influenced the mutagenic activity of the compounds. The ortho isomer exhibited a poorer mutagenic effect than meta and this was found to be a weaker mutagen than para. The presence of metabolic activation enzymes in the test system induced a further increase in his+ revertants, in strains TA100 and TA1535, which is consistent with the findings for melphalan, a cancer chemotherapeutic agent with a chemical structure similar to that of the isomers tested.
在沙门氏菌/微粒体诱变性试验中，对N,N-双(2-氯乙基)氨基肉桂酸的邻、间、对异构体诱变鼠伤寒沙门氏菌菌株的能力进行了测试。该研究的目的是确定这三种异构体之间的构效关系。在TA100和TA1535菌株中，这些药物被发现可诱导碱基对替换，导致组氨酸营养缺陷型回复突变体呈剂量依赖性增加。研究表明，取代基的位置影响了化合物的诱变活性。邻位异构体的诱变作用比间位异构体弱，且被发现是比对位异构体更弱的诱变剂。测试系统中代谢激活酶的存在导致TA100和TA1535菌株中的组氨酸营养缺陷型回复突变体进一步增加，这与美法仑的研究结果一致，美法仑是一种化学结构与所测试异构体相似的癌症化疗药物。
