Regulation of cytochrome P450 2B1/2 mRNAs by Kepone (chlordecone) and potent estrogens in primary cultures of adult rat hepatocytes on Matrigel

Toxicology Letters
T A KocarekP S Guzelian

Abstract

We previously reported that when primary cultures of rat hepatocytes were treated with phenobarbital (PB) or one of several organochlorine pesticides, including Mirex, there was co-induction of cytochrome P450 2B1 and 2B2 mRNAs and immunoreactive proteins, whereas Kepone selectively induced 2B2 (Kocarek et al. (1991) Mol. Pharmacol. 40, 203-210). Indeed, Kepone treatment actively suppressed induction of 2B1 and 2B2 mRNAs in hepatocytes cotreated with phenobarbital. Because Kepone differs chemically from Mirex only in the replacement of 2 chlorine atoms with a ketone group, which exists in aqueous solution as a gem-diol and appears to confer weak estrogenic properties, we treated hepatocyte cultures with one of 3 potent estrogens, beta-estradiol, 17 alpha-ethinylestradiol or diethylstilbestrol. Treatment with each of these estrogens induced 2B1 and 2B2 mRNA only at very high doses (10(-4) M). Beta-Estradiol (10(-4) M) treatment also induced 2B1/2 mRNA in hepatocyte cultures prepared from a prepubescent female rat. The anti-estrogen tamoxifen failed to reverse 2B1/2 mRNA induction following beta-estradiol or Kepone treatment of adult hepatocyte cultures. High doses of beta-estradiol or 17 alpha-ethinylestradiol failed to induce 2...Continue Reading

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Citations

Jun 3, 2000·Annual Review of Pharmacology and Toxicology·G L Plaa
Jan 15, 2005·Toxicology in Vitro : an International Journal Published in Association with BIBRA·P F DehnA Thenappan
Jul 14, 2016·Environmental Health : a Global Access Science Source·Vincent NedellecWilliam Dab
Feb 17, 2001·Journal of Applied Toxicology : JAT·R PoonI Chu
Oct 23, 2004·Drug Metabolism and Pharmacokinetics·Teruo MurakamiMikihisa Takano
Jan 27, 2007·Clinical Pharmacokinetics·Hongjian ZhangA David Rodrigues

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