Metabolism of benzo(c)chrysene by rat liver enzymes
Metabolism of the weak carcinogen benzo(c)chrysene by microsomes and by a purified system reconstituted with cytochrome P-450c and epoxide hydrolase has been examined. With microsomes from 3-methylcholanthrene-treated rats, the hydrocarbon is metabolized at a rate of 6.9 nmoles/min/nmole of cytochrome P-450 as compared to 0.86 for control and 0.65 for phenobarbital-treated rats. Dihydrodiols are the major metabolites, accounting for 50-70% of the total metabolism. The K-region 7,8-dihydrodiol is the principal metabolite while the benzo-ring 1,2- and 9,10 dihydrodiols, precursors to potentially tumorigenic bay-region epoxides are formed in much smaller amounts. The bay-region 3,4-dihydrodiol accounts for 10% of the total metabolites, except in the case of the reconstituted system. The K-region 7,8-dihydrodiol and the benzo-ring 1,2- and 9,10-dihydrodiols are formed with highest enantiomeric purity by microsomes from 3-methylcholanthrene-treated rats. In the case of the K-region dihydrodiol, the (7S,8S)-enantiomer predominates, however in the benzo-ring dihydrodiols it is the (R,R)-enantiomer which predominates in all three microsomal preparations. Phenols at the 3-, 4- and 9-positions account for the balance of the metabolites.
- Research Organization:
- National Institutes of Health, Bethesda, MD
- OSTI ID:
- 6175341
- Report Number(s):
- CONF-870644-
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 46:6; Conference: 78. annual meeting of the American Society of Biological Chemists conference, Philadelphia, PA, USA, 7 Jun 1987
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
CHRYSENE
METABOLISM
LIVER
METABOLIC ACTIVATION
METABOLITES
MICROSOMES
PHENOBARBITAL
PRECURSOR
PROTEINS
RATS
ANESTHETICS
ANIMALS
ANTICONVULSANTS
AROMATICS
AZINES
BARBITURATES
BODY
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CONDENSED AROMATICS
DIGESTIVE SYSTEM
DRUGS
GLANDS
HETEROCYCLIC COMPOUNDS
HYDROCARBONS
HYPNOTICS AND SEDATIVES
MAMMALS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANOIDS
ORGANS
PYRIMIDINES
RODENTS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology