New Sublines of Chinese Hamster CHL Stably Expressing Human NATI or NAT2 W-Acetyltransferases or Salmonella typhimurium 0-Acetyltransferase: Comparison of the Sensitivities to Nitroarenes and Aromatic Amines Using the in Vitro Micronucleus Test1

New sublines of Chinese hamster CHL cells stably expressing human NATI or NAT2 A'-acetyltransferases or 0-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 A'-acetyltransferase exhibited the highest sensitivity to the ciastogenicities of 1,8-dinitropyrene and 2-nitrofluorene. These results raise the possibility that human NAT2 A'-acetyltransferase is involved in the metabolic activation of 1,8-dinitro pyrene and 2-nitrofluorene. Since human NAT2 A'-acetyltransferase ex hibits a marked genetic polymorphism, the polymorphic status of human A'-acetyltransferase could be a genetic predisposing factor to cancers caused by the nitroarenes. In contrast, the subline expressing 0-acetyltransferase of .V. typhimurium exhibited the highest sensitivity to the clastogenicity of 2-amino-3-methylimidazo[4,5-/]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 hu man 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.