A Tryptophan Pyrolysis Product, 3-Amino-1,4- dimethyl-5H-pyrido4,3-bindole(Trp-P-1) but Not Its Metabolite Induces Apoptosis in Primary Cultured Rat Hepatocytes: Induction of CYP 1A Interfaces Trp-P-1-Induced Apoptosis

摘要

Heterocyclic amines, which are formed during the daily cooking process, are the typical carcinogen and considered to be one of the major causes of human cancer. Their carcinogenic or mutagenic activity has been well studied, but the cytotoxicity to normal cells is little known. Previously, we demonstrated that Trp-P-1 also induces apoptosis to primary cultured rat hepatocytes. However, it is not clear which form, intact Trp-P-1 or its metabolite, induces apoptosis. In the carcinogenic process, the N-hydroxylation of Trp-P-1 catalyzed by cytochrome P450 (CYP) 1A subfamily is necessary to show its carcinogenic effects. In the present study, whether the induction of CYP 1A affects cytotoxic and apoptotic effects of Trp-P-1 was investigated using P-naphthoflavone (β-NF) pretreated rats hepatocytes. Pretreatment with β-NF of rats suppressed Trp-P-1-induced apoptosis in primary cultured hepatocytes. In the same cultures, metabolites of Trp-P-1 were increased. These results suggest that intact Trp-P-1 but not its metabolites induce apoptosis in hepatocytes.