Metabolism of N-phenyl-2-naphthylamine andN-phenyl-1-naphthylamine by rat hepaticmicrosomes and hepatocytes

The carcinogenic antioxidants,N-phenyl-1-naphthylamine (P1NA)and N-phenyl-2-naphthylamine (P2NA) were examined in vitro for biotransformation by rat hepatic microsomes and in freshly isolated hepatocytes. HPLC-analysis of hepatocyte incubations with revealed that phenols were the major metabolites in both cases. P1NA formed one phenolic metabolite only, while incubation with P2NA yielded two phenols identified as 6-hydroxy-P2NA and 4'-hydroxy-P2NA by cochromatography with authentic samples. β-naphthylamine, a metabolite indicating dephenylation of P2NA was not detectable.Metabolism studies with microsomes revealed that the phenols were formed by cytochrome P-450 dependent monooxygenases. Pretreatment of animals with phenobarbital and 3-methylcholanthrene both increased the rate of microsomal metabolism of P1NA and P2NA, indicating that more than one P-450 enzyme mediate the oxygenation reaction. Animal pretreatment with single and repeated doses of P1NA and P2NA did not markedly stimulate metabolism, b