Mechanism-based inactivation of cytochrome P-450 dependent benzo(a)pyrene hydroxylase activity by acetylenic and olefinic polycyclic arylhydrocarbons
Thesis/Dissertation
·
OSTI ID:6543960
A series of aryl acetylenes and aryl olefins have been examined as substrates and inhibitors of cytochrome P-450 dependent monooxygenases in liver microsomes from 5,6-benzoflavone or phenobarbital pretreated rats. 1-Ethynylpyrene (EP), 3-ethynylperylene (EPL), cis- and trans-1-(2-bromo-vinyl)pyrene (c-BVP and t-BVP), and 1-allylpyrene (AP) serve as mechanism-based irreversible inactivators (suicide inhibitors) of benzo(a)pyrene (BP) hydroxylase, while 1-vinyl-pyrene (VP) and phenyl 1-pyrenyl acetylene (PPA) do not cause a detectable suicide inhibition of the BP hydroxylase. The mechanism-based loss of BP hydroxylase activity caused by the aryl acetylenes is not accompanied by a corresponding loss of the P-450 content of the microsomes. In the presence of NADPH, /sup 3/H-labeled EP covalently attached to P-450 isozymes with a measured stoichiometry of one mole of EP per mole of the P-450 heme. The results of the effects of these aryl derivatives in the mammalian cell-mediated mutagenesis assay and toxicity assay show that none of the compounds examined nor any of the their metabolites produced in the incubation system are cytotoxic to V79 cells.
- Research Organization:
- Tulane Univ., New Orleans, LA (USA)
- OSTI ID:
- 6543960
- Country of Publication:
- United States
- Language:
- English
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Thu May 01 00:00:00 EDT 1986
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·
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·
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OSTI ID:7100338
Related Subjects
550501 -- Metabolism-- Tracer Techniques
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACETYLENE
ALKENES
ALKYNES
ANIMALS
BODY
CELL CONSTITUENTS
COVALENCE
DIGESTIVE SYSTEM
ENZYME ACTIVITY
ENZYMES
GLANDS
HAMSTERS
HYDROCARBONS
HYDROXYLASES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIVER
LUNGS
MAMMALS
MICROSOMES
MUTAGEN SCREENING
ORGANIC COMPOUNDS
ORGANOIDS
ORGANS
OXIDOREDUCTASES
RATS
RESPIRATORY SYSTEM
RODENTS
SCREENING
STOICHIOMETRY
TOXICITY
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACETYLENE
ALKENES
ALKYNES
ANIMALS
BODY
CELL CONSTITUENTS
COVALENCE
DIGESTIVE SYSTEM
ENZYME ACTIVITY
ENZYMES
GLANDS
HAMSTERS
HYDROCARBONS
HYDROXYLASES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIVER
LUNGS
MAMMALS
MICROSOMES
MUTAGEN SCREENING
ORGANIC COMPOUNDS
ORGANOIDS
ORGANS
OXIDOREDUCTASES
RATS
RESPIRATORY SYSTEM
RODENTS
SCREENING
STOICHIOMETRY
TOXICITY
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES