Document Detail


Dependence of benzo[a]pyrene metabolic profile on the concentration of cumene hydroperoxide with uninduced and induced rat liver microsomes.
MedLine Citation:
PMID:  3707619     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The effect of cumene hydroperoxide (CHP) in microsomal metabolism of benzo [a]pyrene (BP) was studied using liver microsomes from mature male Wistar rats induced with phenobarbital (PB), 3-methylcholanthrene (MC), Aroclor 1254 or olive oil (uninduced). In contrast to NADPH-supported metabolism, these inducers did not increase the CHP-dependent metabolism. Total BP metabolism was dependent on CHP concentration and was maximal at 0.15 mM, except for PB-induced microsomes, which had a maximum at 0.5 mM CHP. At 0.05 mM CHP, the major metabolites were phenols. However, increasing CHP concentration enhanced the formation of dihydrodiols, quinones and protein-bound BP but reduced phenol production. At and above 0.15 mM CHP, the profile of BP metabolites was essentially constant, with at least 66% quinones but no more than 10% phenols. The effect of CHP on inhibition of phenol formation and enhancement of quinone formation was reversed by preincubation of microsomes with BP or by increasing BP concentration. These results suggest that CHP-dependent metabolism of BP is selectively mediated by constitutive cytochrome P-450 isozyme(s) and that two forms of BP binding sites exist in cytochrome P-450 isozymes and are responsible for the hydroxylation of BP at C-3 and C-6.
Authors:
A K Wong; E Cavalieri; E Rogan
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Biochemical pharmacology     Volume:  35     ISSN:  0006-2952     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  1986 May 
Date Detail:
Created Date:  1986-06-06     Completed Date:  1986-06-06     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1583-8     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Aroclors / pharmacology
Benzene Derivatives / pharmacology*
Benzo(a)pyrene / metabolism*
Chlorodiphenyl (54% Chlorine)
Cytochrome P-450 Enzyme System / physiology
Dose-Response Relationship, Drug
Isoenzymes / physiology
Male
Methylcholanthrene / pharmacology
Microsomes, Liver / metabolism*
Phenobarbital / pharmacology
Rats
Rats, Inbred Strains
Grant Support
ID/Acronym/Agency:
1RO1 CA32376/CA/NCI NIH HHS; CA 36729/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Aroclors; 0/Benzene Derivatives; 0/Isoenzymes; 11097-69-1/Chlorodiphenyl (54% Chlorine); 50-06-6/Phenobarbital; 50-32-8/Benzo(a)pyrene; 56-49-5/Methylcholanthrene; 80-15-9/cumene hydroperoxide; 9035-51-2/Cytochrome P-450 Enzyme System

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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