Journal article
Differential time course of induction of rat liver microsomal cytochrome P-450 isozymes and epoxide hydrolase by Aroclor 1254
Archives of biochemistry and biophysics, Vol.225(1), pp.203-215
1983
DOI: 10.1016/0003-9861(83)90024-3
PMID: 6412631
Abstract
The time course of induction of rat liver microsomal cytochromes
P-450a,
P-450b +
P-450e,
P-450c, and
P-450d and epoxide hydrolase has been determined in immature male rats administered a single large dose [1500 μmol (500 mg)/kg body wt] of the polychlorinated biphenyl mixture Aroclor 1254. Differential regulation of these xenobiotic-metabolizing enzymes was indicated by their characteristic patterns of induction. The rate of induction of cytochrome
P-450a and epoxide hydrolase was relatively slow, and steady-state levels of these enzymes were maintained from approximately Days 9 to 15 after Aroclor 1254 treatment. In contrast, cytochrome
P-450c was maximally induced 2 days after Aroclor 1254 treatment and remained at a constant level through Day 15. Steady-state levels of cytochrome
P-450d, beginning 1 week after Aroclor 1254 treatment, were preceded by a fairly rapid rate of induction and possibly by a small decline from maximal levels observed around Days 4 to 5. Like those of the other cytochrome
P-450 isozymes and epoxide hydrolase, the levels of cytochromes
P-450b +
P-450e were constant from Day 9 to 15 after Aroclor 1254 treatment. However, an unexpected but reproducible decline (~25%) in total cytochrome
P-450 content observed between Days 4 and 9 after Aroclor 1254 treatment principally reflected a dramatic and totally unanticipated decrease (~45%) in the level of cytochromes
P-450b +
P-450e. This transient decline in the level of cytochromes
P-450
b +
P-450e was not due to an unusual effect of a mixture of polychlorinated biphenyls, since identical results were obtained with two individual congeners, namely 2,3,4,5,4′-penta- and 2,3,4,5,3′,4′-hexachlorobiphenyl, that induced the same isozymes as Aroclor 1254. In contrast, when rats were treated with 2,4,5,2′,4′,5′-hexachlorobiphenyl, which induces cytochromes
P-450a and
P-450b +
P-450e and epoxide hydrolase but not cytochromes
P-450c or
P-450d, maximal levels of cytochromes
P-450b +
P-450e were attained on Day 4 and no decrease was observed over the next 11 days. These results suggest that there may be an interaction in the regulation of induction of certain individual cytochrome
P-450 isozymes.
Details
- Title: Subtitle
- Differential time course of induction of rat liver microsomal cytochrome P-450 isozymes and epoxide hydrolase by Aroclor 1254
- Creators
- Andrew Parkinson - Department of Biochemistry and Drug Metabolism, Hoffmann-La Roche Inc., Nutley, New Jersey 07110, U.S.APaul E Thomas - Department of Biochemistry and Drug Metabolism, Hoffmann-La Roche Inc., Nutley, New Jersey 07110, U.S.ADene E Ryan - Department of Biochemistry and Drug Metabolism, Hoffmann-La Roche Inc., Nutley, New Jersey 07110, U.S.ALinda M Reik - Department of Biochemistry and Drug Metabolism, Hoffmann-La Roche Inc., Nutley, New Jersey 07110, U.S.AStephen H Safe - Department of Veterinary Physiology and Pharmacology, Texas A & M University, College Station, Texas 77843 U.S.ALarry W Robertson - Department of Veterinary Physiology and Pharmacology, Texas A & M University, College Station, Texas 77843 U.S.AWayne Levin - Department of Biochemistry and Drug Metabolism, Hoffmann-La Roche Inc., Nutley, New Jersey 07110, U.S.A
- Resource Type
- Journal article
- Publication Details
- Archives of biochemistry and biophysics, Vol.225(1), pp.203-215
- Publisher
- Elsevier Inc
- DOI
- 10.1016/0003-9861(83)90024-3
- PMID
- 6412631
- ISSN
- 0003-9861
- eISSN
- 1096-0384
- Language
- English
- Date published
- 1983
- Academic Unit
- Occupational and Environmental Health
- Record Identifier
- 9984002404902771
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