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.
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.
Watanabe
M
M
Division of Genetics and Mutagenesis, National Institute of Health Sciences, Tokyo, Japan.
Matsuoka
A
A
Yamazaki
N
N
Hayashi
M
M
Deguchi
T
T
Nohmi
T
T
Sofuni
T
T
D000123:Acetyltransferases; D000217:Acyltransferases / Q000096:biosynthesis*; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000096:biosynthesis*; D001483:Base Sequence; D001711:Biotransformation; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D005449:Fluorenes / Q000378:metabolism / Q000633:toxicity*; D015870:Gene Expression; D005798:Genes, Bacterial; D006801:Humans; D007700:Kinetics; D015162:Micronucleus Tests; D008969:Molecular Sequence Data; D009153:Mutagens / Q000378:metabolism / Q000633:toxicity*; D009838:Oligodeoxyribonucleotides; D010957:Plasmids; D011721:Pyrenes / Q000378:metabolism / Q000633:toxicity*; D011804:Quinolines / Q000378:metabolism / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000201:enzymology*; D014162:Transfection
D005449:Fluorenes; D009153:Mutagens; D009838:Oligodeoxyribonucleotides; D011721:Pyrenes; D011804:Quinolines; C019499:2-nitrofluorene; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; C033310:1,8-dinitropyrene; D000217:Acyltransferases; D000123:Acetyltransferases; C019736:N-hydroxyarylamine O-acetyltransferase; D001191:Arylamine N-Acetyltransferase