Cytochrome P450 2B enzyme induction defect after 2,2',4,4',5,5'-hexachlorobiphenyl treatment in the fa/fa Zucker rat

Peter N Zannikos; Abhik M Bandyopadhyay; Larry W Robertson; Robert A Blouin

doi:10.1016/S0022-3565(25)38649-0

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Cytochrome P450 2B enzyme induction defect after 2,2',4,4',5,5'-hexachlorobiphenyl treatment in the fa/fa Zucker rat

Journal article

Peer reviewed

Cytochrome P450 2B enzyme induction defect after 2,2',4,4',5,5'-hexachlorobiphenyl treatment in the fa/fa Zucker rat

Peter N Zannikos, Abhik M Bandyopadhyay, Larry W Robertson and Robert A Blouin

The Journal of pharmacology and experimental therapeutics, Vol.268(3), pp.1565-1570

03/1994

DOI: 10.1016/S0022-3565(25)38649-0

PMID: 8138968

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Abstract

The present study describes the effects of 2,2',4,4',5,5'-hexachlorobiphenyl, a "phenobarbital-like" inducer of hepatic cytochrome P450, on the CYP2B1 and CYP2B2 enzymes in the phenotypically obese fa/fa Zucker rat. The fa/fa Zucker rat demonstrated a markedly lower level of CYP2B1/2B2 enzyme induction, as indicated by reduced enzyme activity (testosterone 16 beta-hydroxylation and pentoxyresorufin O-dealkylation), protein concentration (Western blot), and mRNA (slot blot) than the lean Fa/? rodents after in vivo treatment with 2,2',4,4',5,5'-hexachlorobiphenyl. A primary hepatocyte cell culture system was used to control for possible differences in the disposition of 2,2',4,4',5,5'-hexachlorobiphenyl and hormonal dissimilarity between obese and lean Zucker rats. In agreement with the in vivo study, hepatocytes from fa/fa Zucker rats treated with 2,2',4,4',5,5'-hexachlorobiphenyl exhibited a poor induction response based on measurement of CYP2B1/2B2 mRNA. These data are similar to those reported earlier that demonstrate resistance of the CYP2B1/2B2 genes to the inductive effects of phenobarbital in fa/fa Zucker rats. Apparently a genetic defect in obese Zucker rats impairs the increase in CYP2B1/2B2 gene transcription after treatment with phenobarbital as well as 2,2',4,4',5,5'-hexachlorobiphenyl. This study provides evidence that phenobarbital and "phenobarbital-like" inducers share a common cellular element(s) in the induction process of the CYP2B1/2B2 enzymes.

Steroid Hydroxylases - metabolism

Oligodeoxyribonucleotides

Liver - enzymology

Polychlorinated Biphenyls - pharmacology

Cells, Cultured

Body Weight - drug effects

Cytochrome P-450 Enzyme System - metabolism

Molecular Sequence Data

Rats

Male

RNA, Messenger - metabolism

Rats, Zucker

Organ Size - drug effects

Animals

Liver - drug effects

Base Sequence

Cytochrome P-450 Enzyme System - biosynthesis

Cytochrome P-450 Enzyme System - genetics

Enzyme Induction - drug effects

Liver - cytology

Aryl Hydrocarbon Hydroxylases

Steroid Hydroxylases - biosynthesis

Steroid Hydroxylases - genetics

Details

Title: Subtitle: Cytochrome P450 2B enzyme induction defect after 2,2',4,4',5,5'-hexachlorobiphenyl treatment in the fa/fa Zucker rat
Creators: Peter N Zannikos - Division of Pharmacology and Experimental Therapeutics, College of Pharmacy, University of Kentucky, Lexington
Abhik M Bandyopadhyay
Larry W Robertson
Robert A Blouin
Resource Type: Journal article
Publication Details: The Journal of pharmacology and experimental therapeutics, Vol.268(3), pp.1565-1570
Publisher: United States
DOI: 10.1016/S0022-3565(25)38649-0
PMID: 8138968
ISSN: 0022-3565
eISSN: 1521-0103
Grant note: GM42058 / NIGMS NIH HHS
Language: English
Date published: 03/1994
Academic Unit: Occupational and Environmental Health
Record Identifier: 9984002305402771

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