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

作　　者：Thomas Wolff 

机构地区：[1]Institute for Toxikologie, Gesellchaft for Strahlen-und Umweltforchung, Monchen, D-8042 Neuherberg, Germany

出　　处：《Journal of Environmental Sciences》1992年第1期74-83,共10页环境科学学报（英文版）

摘　　要：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, but induced ethylmorphine demethylatior. in males and females and benzo (a)pyrene hydroxylation in females.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, but induced ethylmorphine demethylatior. in males and females and benzo (a)pyrene hydroxylation in females.

关 键 词：N-phenyl-2-naphthylamine N-phenyl-1-naphthylamine hepatocytes. 

分 类 号：X[环境科学与工程]