Evoking cytochrome P450 1A activity interferes with apoptosis induced by 3-amino-1,4-dimethyl-5H-pyrido [4,3-b]indole (Trp-P-1) in rat hepatocytes under the ex vivo system.
3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) is known as a dietary carcinogen and it requires metabolic activation by cytochrome P450 (CYP) 1A subfamily to have carcinogenicity. On the other hand, our previous report demonstrated that Trp-P-1 induces apoptosis in primary cultured rat hepatocytes, but the metabolically activated Trp-P-1 added extracelluarly to hepatocytes did not induce apoptosis. In this study, we focused on the intracellular status of CYPs and investigated apoptotic events induced by Trp-P-1 using hepatocytes isolated from rats treated with three chemical inducers for CYPs. In cultured hepatocytes from rats treated with 3-methylchoranthrene, which mainly induces CYP 1A, Trp-P-1-induced apoptosis was suppressed. In the same cultures, intact Trp-P-1 was decreased and its metabolites were increased. Phenobarbital and pyridine did not affect Trp-P-1-induced apoptosis. These results suggested that evoking CYP 1A activity might interfere with apoptosis induced by Trp-P-1 in rat hepatocytes under the ex vivo system.
Shiotani
Bunsyo
B
Division of Life Science, Graduate School of Science and Technology, Kobe University, Japan.
Nonaka
Yuji
Y
Kanazawa
Kazuki
K
Danno
Gen-ichi
G
Ashida
Hitoshi
H
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002243:Carbolines / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004789:Enzyme Activation; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D002243:Carbolines; D003577:Cytochrome P-450 Enzyme System; C019132:3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole