Biphenyl metabolism by rat liver microsomes. Regioselective effects of inducers, inhibitors, and solvents
The effects of the inducers phenobarbital and 3-methylcholanthrene, the inhibitors 7,8-benzoflavone and 1-benzyl-imidazole, and the solvents methanol, acetone, and dimethyl sulfoxide on the 2-, 3-, and 4-hydroxylation of biphenyl and the O-de-ethylation of 7-ethoxycoumarin by rat liver microsomes were examined. Phenobarbital pretreatment primarily induced 2- and 3-hydroxylation, the latter most dramatically. 3-Methylcholanthrene pretreatment induced 2- and 3-hydroxylation to similar extents. The inhibitors and solvents had regioselective effects on biphenyl metabolism that were characteristic of the uninduced, phenobarbital-induced, and 3-methylcholanthrene-induced microsomes. The presence of multiple forms of cytochrome P-450 in uninduced microsomes is indicated by the regioselective effects of the solvents and the inhibitors. The 3-methylcholanthrene-dependent increases in 2- and 3-hydroxylation appear due to induction of a single form of cytochrome P-450, as indicated by similar dose-response relationships and similar changes in sensitivitty to the inhibitors. The phenobarbital-dependent increases in 2- and 3-hydroxylation appear due to the induction of two forms of cytochrome P-450, as indicated by different changes in sensitivity to the effects of dimethyl sulfoxide and 7,8-benzoflavone. The results indicate that examination of the regioselectivity of biphenyl metabolism is a useful approach for characterizing microsomal mono-oxygenases, and they suggest that the approach may also be useful in the characterization of purified mono-oxygenase systems. (JMT)
- Research Organization:
- Argonne National Lab., IL
- DOE Contract Number:
- W-31109-ENG-38
- OSTI ID:
- 5236504
- Journal Information:
- Drug Metab. Dispos.; (United States), Journal Name: Drug Metab. Dispos.; (United States) Vol. 9:3; ISSN DMDSA
- Country of Publication:
- United States
- Language:
- English
Similar Records
3-(Trifluoromethyl)-3-(m-(/sup 125/I)iodophenyl)diazirine photolabels a substrate-binding site of rat hepatic cytochrome P-450 form PB-4
Heterogeneity of cytochrome P-450s induced by polychlorinated biphenyls. [Aroclor 1254]
Related Subjects
550900 -- Pathology
560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACETONE
ALCOHOLS
ANESTHETICS
ANIMALS
ANTICONVULSANTS
AROMATICS
AZINES
AZOLES
BARBITURATES
BENZIMIDAZOLES
BIOLOGICAL EFFECTS
BIPHENYL
BODY
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CYTOCHROMES
DIGESTIVE SYSTEM
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ENZYMES
FLAVENOIDS
FLAVONES
GLANDS
HETEROCYCLIC COMPOUNDS
HYDROCARBONS
HYDROXY COMPOUNDS
HYDROXYLATION
HYPNOTICS AND SEDATIVES
IMIDAZOLES
KETONES
LIVER
MAMMALS
METABOLISM
METABOLITES
METHANOL
MICROSOMES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANOIDS
ORGANS
OXIDOREDUCTASES
OXYGENASES
PHENOBARBITAL
PIGMENTS
POLYCYCLIC AROMATIC HYDROCARBONS
PYRIMIDINES
RATS
RODENTS
SENSITIVITY
SOLVENTS
VERTEBRATES