New sublines of Chinese hamster CHL stably expressing human NAT1 or NAT2 N-acetyltransferases or Salmonella typhimurium O-acetyltransferase: comparison of the sensitivities to nitroarenes and aromatic amines using the in vitro micronucleus test.

Abstract

New sublines of Chinese hamster CHL cells stably expressing human NAT1 or NAT2 N-acetyltransferases or O-acetyltransferase of Salmonella typhimurium were established, and their sensitivities to carcinogenic nitroarenes and aromatic amines were compared using the in vitro micronucleus test. The subline expressing human NAT2 N-acetyltransferase exhibited the highest sensitivity to the clastogenicities of 1,8-dinitropyrene and 2-nitrofluorene. These results raise the possibility that human NAT2 N-acetyltransferase is involved in the metabolic activation of 1,8-dinitro-pyrene and 2-nitrofluorene. Since human NAT2 N-acetyltransferase exhibits a marked genetic polymorphism, the polymorphic status of human N-acetyltransferase could be a genetic predisposing factor to cancers caused by the nitroarenes. In contrast, the subline expressing O-acetyltransferase of S. typhimurium exhibited the highest sensitivity to the clastogenicity of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) when the microsomes prepared from rat liver were present. This suggests that O-acetyltransferase of S. typhimurium has a higher ability to activate IQ than do the human acetyltransferases. Acetyltransferase enzymes of human enteric bacteria might contribute to the metabolic activation of IQ. The sublines could provide a new tool for investigation of the mechanism of metabolic activation and for assessment of cancer risk of nitroarenes and aromatic amines to humans.