Evoking cytochrome P450 1A activity interferes with apoptosis induced by 3-amino-1,4-dimethyl-5 H-pyrido (4,3-b)indole (Trp-P-1) in rat hepatocytes under the ex vivo system
2002
Shiotani, B. (Kobe Univ. (Japan)) | Nonaka, Y. | Kanazawa, K. | Danno, G. | Ashida, H.
3-Amino-1, 4-dimethyl-5H-pyrido [4, 3-b]indole (Trp-P-l) is known as a dietary carcinogen and it requires metabolic activation by cytochrome P450 (GYP) 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.
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