Metabolism of benzo(a)pyrene with isolated hepatocytes and the formation and degradation of DNA-binding derivatives. [3-methylcholanthrene]
The metabolism of (/sup 14/C)benzo(a)pyrene with isolated hepatocytes from 3-methylcholanthrene-treated rats was examined with the aid of high pressure liquid chromatography. Covalent binding of (/sup 3/H)benzo(a)pyrene metabolites to the intracellular DNA was investigated. The effects of ..cap alpha..-naphthoflavone, salicylamide, trichloropropene oxide, and diethylmaleate, individually or combined, on the metabolism and covalent DNA binding of benzo(a)pyrene were determined. The results indicate that the initial organic-soluble metabolites were arene oxides, phenols, quinones, and dihydrodiols and that these were subsequently converted to relatively polar, organic-soluble nonconjugated and sulfate-conjugated metabolites and to aqueous-soluble nonconjugated and glucuronide- and glutathione-conjugated metabolites. ..cap alpha..-Naphthoflavone inhibited the formation of benzo(a)pyrene metabolites that covalently bound to hepatocyte DNA, while the binding was stimulated by salicylamide, trichloropropene oxide, or diethylmaleate. Our observations indicate that benzo(a)pyrene-oxide hydration and glutathione conjugation, and glucuronide and sulfate conjugation of hydroxylated benzo(a)pyrene metabolites operate in concert to detoxify electrophilic DNA-binding benzo(a)pyrene metabolites in isolated hepatocytes. The degree of covalent binding of benzo(a)pyrene to the nuclear DNA of isolated hepatocytes seems thus to be correlated with the production of electrophilic benzo(a)pyrene metabolites and the rate of their disposal by epoxide hydratase and conjugation reactions.
- Research Organization:
- Karolinska Institutet, Stockholm
- OSTI ID:
- 5140403
- Journal Information:
- J. Biol. Chem.; (United States), Journal Name: J. Biol. Chem.; (United States) Vol. 252:18; ISSN JBCHA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
AROMATICS
BENZOPYRENE
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CARBON 14
CARBON ISOTOPES
CARCINOGENS
CHEMICAL BONDS
CHOLANTHRENE
CONDENSED AROMATICS
DIGESTIVE SYSTEM
DNA
EVEN-EVEN NUCLEI
GLANDS
HYDROCARBONS
ISOTOPES
LABELLED COMPOUNDS
LIGHT NUCLEI
LIVER
MAMMALS
METABOLISM
NUCLEI
NUCLEIC ACIDS
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANS
OXYGEN COMPOUNDS
POLYCYCLIC AROMATIC HYDROCARBONS
RADIOISOTOPES
RATS
RODENTS
SULFATES
SULFUR COMPOUNDS
VERTEBRATES
YEARS LIVING RADIOISOTOPES