The possible role of acetyltransferase in the induction of cytogenetic effects by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in cultured Chinese hamster cells.
When metabolically activated, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a heterocyclic amine isolated from cooked food, is clastogenic in cultured Chinese hamster and human cells. Secondary metabolites of PhIP are formed via acetyltransferase (AT) and sulfotransferase (ST) activity; however, which is responsible for its clastogenic effect is unknown. We addressed this question. We used a parental Chinese hamster lung cell line and three sublines transfected with different AT genes to test the clastogenic (i.e., micronucleus-inducing) effects of metabolically activated PhIP and 7,12-dimethylbenz[a]anthracene (DMBA) in the presence and absence of pentachlorophenol (PCP), a ST inhibitor. PhIP was significantly more clastogenic in the three AT-enriched sublines than in the parental line (p < 0.001). DMBA (a ST-activated mutagen), on the other hand, equally induced MNs in all the cell lines. When PCP was added to the test system, the MN-induction ability of DMBA, but not of PhIP, decreased significantly (p < 0.001). These findings strongly suggest that PhIP clastogenicity is due to AT activity and not to ST activity.
Otsuka
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C
Chromosome Research Center (CRC), Olympus Optical Co., Ltd., Tokyo, Japan.
Miura
K F
KF
Ishidate
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M
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004347:Drug Interactions; D006801:Humans; D007093:Imidazoles / Q000633:toxicity*; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D010416:Pentachlorophenol / Q000494:pharmacology
D007093:Imidazoles; D009153:Mutagens; D015127:9,10-Dimethyl-1,2-benzanthracene; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D010416:Pentachlorophenol; D000123:Acetyltransferases