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Benzo[a]pyrene metabolism in the Mongolian gerbil: influence of chlordecone and mirex induction

L S Crouch1, R E Ebel

  • 1Department of Biochemistry and Nutrition, Virginia Polytechnic Institute and State University, Blacksburg 24061.

Xenobiotica; the Fate of Foreign Compounds in Biological Systems
|July 1, 1987
PubMed

Insights

Gerbil liver enzymes metabolize benzo[a]pyrene (BP) differently based on induction. Phenobarbital (PB), chlordecone, and mirex induce similar P450 enzymes, while 3-methylcholanthrene (3-MC) induces distinct enzymes. Only PB increased epoxide hydrolase.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Toxicology

Background:

  • Benzo[a]pyrene (BP) is a polycyclic aromatic hydrocarbon metabolized by hepatic enzymes.
  • Enzyme induction can alter the metabolism of xenobiotics like BP.
  • Cytochromes P-450 (CYP) are key enzymes involved in BP metabolism.

Purpose of the Study:

  • To investigate the effects of various inducers on gerbil hepatic microsomal metabolism of benzo[a]pyrene.
  • To characterize the specific cytochrome P-450 isozymes involved in BP metabolism following induction.
  • To assess the impact of inducers on microsomal epoxide hydrolase activity.

Main Methods:

  • Gerbil hepatic microsomes were isolated following induction with phenobarbital (PB), chlordecone, mirex, or 3-methylcholanthrene (3-MC).
  • Benzo[a]pyrene metabolism was assessed by measuring BP-hydroxylase activity.
  • The influence of alpha-naphthoflavone (alpha-NF) and BP-metabolite profiles were used to differentiate CYP isozymes.

Main Results:

  • Induction with PB, chlordecone, or mirex resulted in similar alterations in BP metabolism, suggesting the involvement of similar CYP isozymes.
  • Cytochromes P-450 in control and 3-MC-induced microsomes differed from each other and from those induced by PB, chlordecone, or mirex.
  • Only phenobarbital (PB) induction significantly increased microsomal epoxide hydrolase activity.

Conclusions:

  • Phenobarbital, chlordecone, and mirex induce a common set of CYP isozymes responsible for BP metabolism in gerbils.
  • 3-methylcholanthrene induces a distinct set of CYP isozymes, differing from those induced by the other agents.
  • Phenobarbital is the only inducer tested that also enhances microsomal epoxide hydrolase activity.

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