Induction and post-transcriptional suppression of hepatic cytochrome P450 1A1 by 3,3',4,4'-tetrachlorobiphenyl

Biochemical Pharmacology
R D WhiteJ J Stegeman

Abstract

3,3',4,4'-Tetrachlorobiphenyl (TCB) can induce and inhibit cytochrome P450 1A1 (CYP1A1) in vertebrates. TCB may also suppress CYP1A1 protein levels, but the mechanism is unknown. This study examined transcriptional and translational aspects of hepatic CYP1A1 regulation in the fish scup (Stenotomus chrysops) given single intraperitoneal injections of low (0.1 mg/kg) or high (5 mg/kg) doses of TCB, and sampled over 16 days. The low dose strongly induced hepatic CYP1A1 mRNA (25-fold), protein (12-fold), and activity [ethoxyresorufin O-deethylase (EROD)] (15-fold). The high dose also strongly induced CYP1A1 mRNA (29-fold), in a pattern like that at the low dose, but microsomal CYP1A1 protein content was induced only 4-fold and EROD rates were near control levels. Both TCB doses caused similar increases in microsomal cytochrome b5 content, and in rates of NADPH-cytochrome c (P450) reductase and UDP-glucuronosyltransferase (with p-nitrophenol). The contents of CYP forms other than CYP1A1 (putative CYP2B or CYP3A) were only weakly affected by TCB at either dose. The strong and largely specific post-transcriptional suppression of CYP1A1 content was associated with high concentrations of TCB measured in the liver. Incubation of scup hep...Continue Reading

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Citations

Feb 11, 1999·Comparative Biochemistry and Physiology. Part C, Pharmacology, Toxicology & Endocrinology·D R Buhler, J L Wang-Buhler
Jan 16, 2002·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·J J SchlezingerJ J Stegeman
Feb 1, 2003·Environmental Toxicology and Pharmacology·Ron van der OostNico P E Vermeulen
Jul 11, 2012·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Ben F BrammellAdria A Elskus
Apr 25, 2015·Environmental Science and Pollution Research International·Paula Suares-RochaMaria Aparecida Marin-Morales
Aug 2, 2011·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Chang ZhouJun-Fang Zhou
Jan 21, 2015·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Tineke SlootwegMarkus Liebig
Aug 24, 2000·Critical Reviews in Toxicology·J J WhyteD E Tillitt

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