Interrelationships in mice of antipyrine half-life, hepatic monooxygenase activities and liver S9-mediated mutagenicity of aflatoxin B1, benzo[alpha]pyrene 7,8-dihydrodiol, 2-acetylaminofluorene and N-nitrosomorpholine.
To evaluate the predictive value of serum antipyrine half-life AP(T1/2) as an index of hepatic carcinogen metabolism, groups of C57BL/6 and DBA/2 mice were treated with various inducers and inhibitors of cytochrome P-450-dependent monooxygenases (pregnenolone-16 alpha-carbonitrile (PCN), phenobarbital (PB), 5,6-benzoflavone (5,6-BF), 3-methylcholanthrene (MC), disulfiram (DIS), 7,8-BF). Groups of mice were also given ethanol (3% in drinking water) for 12 days. Within each group, mean serum AP-(T1/2) was compared with (i) the in vitro activity of hepatic microsomal benzo[alpha]pyrene (BP) 3-hydroxylase, 2-acetylaminofluorene (AAF)-N-hydroxylase and aldrin monooxygenase, and (ii) the liver S9-mediated mutagenicity of aflatoxin B1 (AFB), trans-7,8-dihydro-7,8-dihydroxybenzo[alpha]pyrene (BP 7,8-diol), 2-acetylaminofluorene and N-nitrosomorpholine (NMOR) in Salmonella typhimurium strains. Serum AP(T1/2) was only correlated negatively with the activity of BP 3-hydroxylase (P less than 0.001) and aldrin monooxygenase (P less than 0.001). No statistically significant correlation was found between serum AP(T1/2) and liver S9-mediated mutagenicity for any of the four carcinogens. On the basis of these results, we conclude that serum AP(T1/2) may not be a reliable index of the capacity of liver to convert carcinogens into reactive intermediates.
D015073:2-Acetylaminofluorene / Q000494:pharmacology; D016604:Aflatoxin B1; D000348:Aflatoxins / Q000494:pharmacology; D000818:Animals; D000983:Antipyrine / Q000097:blood*; D001580:Benzopyrenes / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System; D004101:Dihydroxydihydrobenzopyrenes; D005260:Female; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009153:Mutagens / Q000494:pharmacology; D009602:Nitrosamines / Q000494:pharmacology; D010105:Oxygenases / Q000378:metabolism*
D000348:Aflatoxins; D001580:Benzopyrenes; D004101:Dihydroxydihydrobenzopyrenes; D009153:Mutagens; D009602:Nitrosamines; C017228:benzo(a)pyrene 7,8-dihydrodiol; C002741:N-nitrosomorpholine; D003577:Cytochrome P-450 Enzyme System; D015073:2-Acetylaminofluorene; D016604:Aflatoxin B1; D010105:Oxygenases; D000983:Antipyrine