Binding of benzo(a)pyrene to DNA by cytochrome P-450 catalyzed one-electron oxidation in rat liver microsomes and nuclei

Journal Article · Tue May 22 00:00:00 EDT 1990 · Biochemistry; (United States)

DOI:https://doi.org/10.1021/bi00472a011· OSTI ID:5457538

Cavalieri, E L; Rogan, E G; Devanesan, P D; Cremonesi, P ^[1]; Cerny, R L; Gross, M L ^[2]; Bodell, W J ^[3]

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1. Univ. of Nebraska Medical Center, Omaha (USA)
2. Univ. of Nebraska, Lincoln (USA)
3. 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), Journal Name: Biochemistry; (United States) Vol. 29:20; ISSN 0006-2960; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

3-METHYLCHOLANTHRENE
550201 -- Biochemistry-- Tracer Techniques
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDUCTS
ANIMALS
AROMATICS
BENZOPYRENE
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMISTRY
BIOLOGICAL EFFECTS
BODY
CELL CONSTITUENTS
CELL NUCLEI
CHEMICAL REACTIONS
CHEMISTRY
CHROMATOGRAPHY
CONDENSED AROMATICS
CYTOCHROME OXIDASE
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DNA
DNA ADDUCTS
ENZYMES
GLANDS
HAEM DEHYDROGENASES
HYDROCARBONS
HYDROGEN COMPOUNDS
ISOTOPES
LIGHT NUCLEI
LIQUID COLUMN CHROMATOGRAPHY
LIVER
MAMMALS
MICROSOMES
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
OXIDATION
OXIDOREDUCTASES
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
POLYCYCLIC AROMATIC HYDROCARBONS
RADIOISOTOPES
RATS
RIBOSOMES
RODENTS
SEPARATION PROCESSES
TRITIUM COMPOUNDS
VERTEBRATES