Different effects of chemicals on metabolism of N-nitrosamines in rat liver.
The effects of phenobarbital (PB), 3-methylcholanthrene (MC), pyrazole (PY) and ethanol (EtOH) pretreatment on N-nitrosodimethylamine (NDMA), N-nitrosobutylmethylamine (NBMA) and N-nitrosomethylbenzylamine (NMBzA) metabolism were examined in rats. In isolated hepatocytes, PB increased the metabolic decomposition of NBMA and NMBzA, and MC increased that of NBMA; PY and EtOH increased only that of NDMA. In studies of hepatic microsomal dealkylation, PB increased NBMA debutylation and NMBzA debenzylation, and MC increased NBMA debutylation; PY and EtOH increased NDMA demethylation selectively. Several cytochrome P450 (P450) species were active in dealkylating nitrosamines, indicating that the organ-specific carcinogenicity of nitrosamines might be changed by various P450 inducers.
Kawanishi
T
T
Biological Safety Research Center, National Institute of Hygienic Sciences, Japan.
Ohno
Y
Y
Takahashi
A
A
Takanaka
A
A
Omori
Y
Y
D000818:Animals; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008748:Methylcholanthrene / Q000494:pharmacology; D009602:Nitrosamines / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats
D009602:Nitrosamines; D011720:Pyrazoles; D000431:Ethanol; C031280:pyrazole; D008748:Methylcholanthrene; C014707:nitrosobenzylmethylamine; D004128:Dimethylnitrosamine; D010634:Phenobarbital