Binding of benzo(a)pyrene to DNA by cytochrome P-450 catalyzed one-electron oxidation in rat liver microsomes and nuclei
- Univ. of Nebraska Medical Center, Omaha (USA)
- Univ. of Nebraska, Lincoln (USA)
- Univ. of California, San Francisco (USA)
To investigate whether cytochrome P-450 catalyzes the covalent binding of substrates to DNA by one-electron oxidation, the ability of both uninduced and 3-methylcholanthrene (MC) induced rat liver microsomes and nuclei to catalyze covalent binding of benzo(a)pyrene (BP) to DNA and formation of the labile adduct 7-(benzo(a)pyren-6-yl)guanine (BP-N7Gua) was investigated. In the various systems studied, 1-9 times more BP-N7Gua adduct was isolated than the total amount of stable BP adducts in the DNA. The specific cytochrome P-450 inhibitor 2-((4,6-dichloro-o-biphenyl)oxy)ethylamine hydrobromide (DPEA) reduced or eliminated BP metabolism, binding of BP to DNA, and formation of BP-N7Gua by cytochrome P-450 in both microsomes and nuclei. The effects of the antioxidants cysteine, glutathione, and p-methoxythiophenol were also investigated. This study represents the first demonstration of cytochrome P-450 mediating covalent binding of substrates to DNA via one-electron oxidation and suggests that this enzyme can catalyze peroxidase-type electron-transfer reactions.
- OSTI ID:
- 5457538
- Journal Information:
- Biochemistry; (United States), Vol. 29:20; ISSN 0006-2960
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
BENZOPYRENE
BIOLOGICAL EFFECTS
CYTOCHROME OXIDASE
BIOCHEMISTRY
DNA ADDUCTS
LIQUID COLUMN CHROMATOGRAPHY
3-METHYLCHOLANTHRENE
CELL NUCLEI
DNA
LIVER
MICROSOMES
OXIDATION
PHOSPHORUS 32
RATS
TRITIUM COMPOUNDS
ADDUCTS
ANIMALS
AROMATICS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CELL CONSTITUENTS
CHEMICAL REACTIONS
CHEMISTRY
CHROMATOGRAPHY
CONDENSED AROMATICS
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
ENZYMES
GLANDS
HAEM DEHYDROGENASES
HYDROCARBONS
HYDROGEN COMPOUNDS
ISOTOPES
LIGHT NUCLEI
MAMMALS
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
OXIDOREDUCTASES
PHOSPHORUS ISOTOPES
POLYCYCLIC AROMATIC HYDROCARBONS
RADIOISOTOPES
RIBOSOMES
RODENTS
SEPARATION PROCESSES
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology
550201 - Biochemistry- Tracer Techniques