Dependence of benzo[a]pyrene metabolic profile on the concentration of cumene hydroperoxide with uninduced and induced rat liver microsomes

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1583-1588
Number of pages6
JournalBiochemical Pharmacology
Volume35
Issue number9
DOIs
StatePublished - May 1 1986

Fingerprint

Metabolome
Benzo(a)pyrene
Liver Microsomes
Liver
Rats
Metabolism
Quinones
Phenols
Phenobarbital
Metabolites
Microsomes
Phenol
Cytochrome P-450 Enzyme System
Isoenzymes
Chlorodiphenyl (54% Chlorine)
cumene hydroperoxide
Hydroxylation
Methylcholanthrene
NADP
Wistar Rats

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

Cite this

@article{67c65d633d8543848245453f0a88c297,
title = "Dependence of benzo[a]pyrene metabolic profile on the concentration of cumene hydroperoxide with uninduced and induced rat liver microsomes",
abstract = "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.",
author = "Wong, {Allan K L} and Ercole Cavalieri and Rogan, {Eleanor G}",
year = "1986",
month = "5",
day = "1",
doi = "10.1016/0006-2952(86)90128-0",
language = "English (US)",
volume = "35",
pages = "1583--1588",
journal = "Biochemical Pharmacology",
issn = "0006-2952",
publisher = "Elsevier Inc.",
number = "9",

}

TY - JOUR

T1 - Dependence of benzo[a]pyrene metabolic profile on the concentration of cumene hydroperoxide with uninduced and induced rat liver microsomes

AU - Wong, Allan K L

AU - Cavalieri, Ercole

AU - Rogan, Eleanor G

PY - 1986/5/1

Y1 - 1986/5/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0022554025&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0022554025&partnerID=8YFLogxK

U2 - 10.1016/0006-2952(86)90128-0

DO - 10.1016/0006-2952(86)90128-0

M3 - Article

VL - 35

SP - 1583

EP - 1588

JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

SN - 0006-2952

IS - 9

ER -