Regulation of constitutive rat hepatic cytochromes P450 by 3-methylcholanthrene

Xenobiotica. 1996 Oct;26(10):995-1012. doi: 10.3109/00498259609167418.


1. Induction of cytochrome P450 (CYP) enzymes of the CYP1A subfamily by aromatic hydrocarbons such as 3-methylcholanthrene (MC) is accompanied by down-regulation of other CYPs that are expressed constitutively in rat liver. 2. We examined the time-course of the effects of MC on the expression of CYP2C11 and 3A2 in the liver of male rats at the catalytic activity, apoprotein and mRNA levels. 3. A single intraperitoneal dose of MC (50 mg/kg) caused an increase in total hepatic microsomal CYP and haem content, and a marked induction of CYP1A1 catalytic activity (7-ethoxyresorufin O-deethylase) and apoprotein. The activity of NADPH-cytochrome P450 reductase was not altered. 4. MC treatment decreased CYP2C11 and 3A catalytic activity (testosterone 16 alpha- and 6 beta-hydroxylase respectively) and apoprotein, and there was a trend for suppression of 2C11 and 3A2 mRNA. Following this initial down-regulation, CYP2C11 catalytic activity and 3A catalytic activity and apoprotein were elevated above control levels. Although CYP2C11 and 3A2 mRNA levels showed a similar trend, these effects did not achieve statistical significance. 5. CYP2C11 and 3A2 appear to be regulated by MC at a pre-translational level. CYP2C11 suppression will serve as a valuable model for study on the mechanisms by which aromatic hydrocarbons act to negatively influence gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aryl Hydrocarbon Hydroxylases*
  • Catalysis
  • Cytochrome P-450 CYP1A1 / metabolism
  • Cytochrome P-450 Enzyme System / biosynthesis
  • Cytochrome P-450 Enzyme System / genetics*
  • Cytochrome P450 Family 2
  • Enzyme Induction / drug effects
  • Female
  • Heme / metabolism
  • Liver / metabolism*
  • Male
  • Methylcholanthrene / pharmacology*
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / metabolism
  • NADPH-Ferrihemoprotein Reductase / metabolism
  • Rats
  • Rats, Inbred F344
  • Receptors, Aryl Hydrocarbon / metabolism
  • Steroid 16-alpha-Hydroxylase*
  • Steroid Hydroxylases / genetics*


  • Receptors, Aryl Hydrocarbon
  • Heme
  • Methylcholanthrene
  • Cytochrome P-450 Enzyme System
  • Steroid Hydroxylases
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C11 protein, rat
  • Cytochrome P-450 CYP1A1
  • Cytochrome P450 Family 2
  • Steroid 16-alpha-Hydroxylase
  • steroid hormone 6-beta-hydroxylase
  • NADPH-Ferrihemoprotein Reductase