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

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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.