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Benzo[a]pyrene metabolism in the Mongolian gerbil: influence of chlordecone and mirex induction
1Department of Biochemistry and Nutrition, Virginia Polytechnic Institute and State University, Blacksburg 24061.
Abstract:
1. The metabolism of benzo[a]pyrene (BP) by gerbil hepatic microsomes is increased following induction by phenobarbital (PB), chlordecone, mirex and 3-methylcholanthrene (3-MC). 2. By several criteria including the influence of alpha-naphthoflavone (alpha-NF) on BP-hydroxylase activity and BP-metabolite profiles, the cytochromes P-450 responsible for benzo[a]pyrene metabolism appear to be similar in microsomes isolated from PB-, chlordecone-, or mirex-treated gerbils. The cytochromes P-450 present in microsomes isolated from control animals and those treated with 3-MC are different from each other and from those present in PB, chlordecone, or mirex microsomes by the same criteria. 3. Of the inducers used, only PB induced microsomal epoxide hydrolase activity.
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.