@article {Zannikos1565, author = {P N Zannikos and A M Bandyopadhyay and L W Robertson and R A Blouin}, title = {Cytochrome P450 2B enzyme induction defect after 2,2{\textquoteright},4,4{\textquoteright},5,5{\textquoteright}-hexachlorobiphenyl treatment in the fa/fa Zucker rat.}, volume = {268}, number = {3}, pages = {1565--1570}, year = {1994}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {The present study describes the effects of 2,2{\textquoteright},4,4{\textquoteright},5,5{\textquoteright}-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{\textquoteright},4,4{\textquoteright},5,5{\textquoteright}-hexachlorobiphenyl. A primary hepatocyte cell culture system was used to control for possible differences in the disposition of 2,2{\textquoteright},4,4{\textquoteright},5,5{\textquoteright}-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{\textquoteright},4,4{\textquoteright},5,5{\textquoteright}-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{\textquoteright},4,4{\textquoteright},5,5{\textquoteright}-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.}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/268/3/1565}, eprint = {https://jpet.aspetjournals.org/content/268/3/1565.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }