Establishment of high sensitive Salmonella tester strains expressing mammalian acetvltransferase and sulfotransferase

我们一直在研究致癌芳香胺在哺乳动物肝脏和沙门氏菌中的代谢活化。本文报道了在哺乳动物肝脏代谢活化中起作用的N，O-乙酰转移酶和磺基转移酶在艾姆斯试验菌株中的缺陷。在这个项目中，我们新建立了两个艾姆斯试验菌株，其中仓鼠芳胺乙酰转移酶和大鼠N-羟基芳胺O-磺基转移酶独立表达。新菌株对环境致癌物（包括N-羟基-2-乙酰氨基芴）的敏感性提高了100-10，000倍。此外，委员会认为，表达乙酰转移酶的菌株对联苯胺表现出高敏感性，而艾姆斯试验菌株对联苯胺没有表现出任何敏感性。乙酰转移酶和磺基转移酶被证明不仅催化芳胺（酰胺）的N-羟基衍生物的活化，而且催化食品-这些结果表明，沙门氏菌艾姆斯试验菌株中哺乳动物酯化酶的表达产生了新的高度敏感的对各种环境致癌物的测试菌株。因此，我们的结论是，这种方法是有用的更预测性的评估环境诱变剂和致癌物。

We have been studying metabolic activation of carcinogenic arylamines in mammalian livers and Salmonella. We reported that N,O-acetyltransferase and sulfotransferase, which playd a role in the metabolic activation in mammalian livers, were deficient in Ames tester strains. In this project, we newly established two Ames tester strains in which hamster arylamine acetyltransferase and rat N-hydroxy arylamine O-sulfotransferase were independently expressed. The new strains were 100-10,000times more sensitive to environmental carcinogens including N-hydroxy-2-acetylaminofluorene. Furthermore, the acetyltransferase-expressing strain showed high sensitivity to benzidine to which no Ames tester strain had showed any sensitivity.The acetyltransferase and the sulfotransferase were shown to catalyze activation of N-hydroxy derivatives of not only arylamine (amide) s but also food-derived pyrolysate carcinogens.These results indicated that the expression of mammalian esterification enzymes in Salmonella Ames tester strain resulted in new highly sensitive tester strains toward various kinds of environmental carcinogens. Thus, we concluded that this kind of approach is useful for the more predictive assessment of environmental mutagens and carcinogens.