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Abstract

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

P N Zannikos, A M Bandyopadhyay, L W Robertson and R A Blouin
Journal of Pharmacology and Experimental Therapeutics March 1994, 268 (3) 1565-1570;
P N Zannikos
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A M Bandyopadhyay
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L W Robertson
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R A Blouin
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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.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 268, Issue 3
1 Mar 1994
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Abstract

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

P N Zannikos, A M Bandyopadhyay, L W Robertson and R A Blouin
Journal of Pharmacology and Experimental Therapeutics March 1, 1994, 268 (3) 1565-1570;

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Abstract

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

P N Zannikos, A M Bandyopadhyay, L W Robertson and R A Blouin
Journal of Pharmacology and Experimental Therapeutics March 1, 1994, 268 (3) 1565-1570;
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