RT Journal Article SR Electronic T1 Genetic Differences in the Aromatic Hydrocarbon-Inducible N-Hydroxylation of 2-Acetylaminofluorene and Acetaminophen-Produced Hepatotoxicity in Mice JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 159 OP 165 VO 11 IS 2 A1 SNORRI S. THORGEIRSSON A1 JAMES S. FELTON A1 DANIEL W. NEBERT YR 1975 UL http://molpharm.aspetjournals.org/content/11/2/159.abstract AB The genetically mediated presence or absence of induction, as well as the magnitude of induction, of aryl hydrocarbon (benzo[a]pyrene) hydroxylase activity is highly correlated (p < 0.001) with the N-hydroxylation of 2-acetylaminofluorene in the livers of C57BL/6N and DBA/2N inbred mice treated with the microsomal enzyme inducers 3-methylcholanthrene, β-naphthoflavone, 2,3,7,8-tetrachlorodibenzo-p-dioxin, and sodium phenobarbital. The extent of hepatotoxicity caused by acetaminophen (p-hydroxyacetanilide) administered intraperitoneally to these two strains of mice is also highly associated with both aromatic hydrocarbon-inducible monooxygenase "activities": aryl hydrocarbon hydroxylase and acetylarylamine N-hydroxylase. We suggest that cytochrome P1450 is involved with the aromatic hydrocarbon-inducible N-hydroxylase activity and that these genetic differences among inbred strains of mice offer a valuable experimental model system for studying the mechanism of hepatotoxicity and carcinogenicity among siblings of a defined genotype.