We have previously reported that quinoline increased the mutation frequency of the cII gene in the liver of lambda/lacZ transgenic mice (Muta™Mouse), and G:C to C:G transversions were the molecular signature of quinoline-induced mutations. 4-Methylquinoline (4-MeQ) has the highest mutagenicity among quinoline and isomeric methylquinolines according to the Ames test using Salmonella typhimurium TA 100, in the presence of rat liver microsomal enzymes. In this report, we examined the effect of 4-MeQ on mutagenesis in the lambda cII gene in the liver of the Muta™Mouse, and we analyzed the sequences of the mutated genes. The mutation frequency of the liver cII gene was seven times higher in 4-MeQ-treated mice than in control mice. Sequence analysis revealed that 4-MeQ primarily induced G:C to C:G transversions (37 of 45). The specificities of 4-MeQ for target organ and mutation pattern were very consistent with those of quinoline. Thus, we showed that 4-MeQ was also genotoxic in the liver of the Muta™Mouse, and as with quinoline, the G:C to C:G transversion was the molecular signature of the 4-MeQ-induced mutations.

我们以前曾报道过，喹啉增加了lambda / lacZ转基因小鼠（Muta™Mouse）肝脏cII基因的突变频率，而G：C向C：G的转化是喹啉诱导的突变的分子特征。根据鼠伤寒沙门氏菌TA 100的Ames试验，在大鼠肝微粒体酶存在下，4-甲基喹啉（4-MeQ）在喹啉和异构甲基喹啉中具有最高的致突变性。在本报告中，我们研究了4-MeQ对Muta™小鼠肝脏中lambda cII基因诱变的影响，并分析了突变基因的序列。肝脏cII的突变频率在接受4-MeQ处理的小鼠中，该基因比对照小鼠高7倍。序列分析表明4-MeQ主要诱导了从G：C到C：G的转化（45中的37）。4-MeQ对靶器官和突变模式的特异性与喹啉非常一致。因此，我们表明4-MeQ在Muta™小鼠的肝脏中也具有遗传毒性，并且与喹啉一样，G：C向C：G的转化是4-MeQ诱导的突变的分子特征。