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

Biosci Biotechnol Biochem. 2002 Feb;66(2):356-62. doi: 10.1271/bbb.66.356.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Carbolines / pharmacology*
  • Cytochrome P-450 Enzyme System / metabolism*
  • Enzyme Activation
  • Hepatocytes / cytology
  • Hepatocytes / drug effects*
  • In Vitro Techniques
  • Male
  • Rats
  • Rats, Wistar

Substances

  • Carbolines
  • Cytochrome P-450 Enzyme System
  • 3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole