Mechanism-based inactivation of cytochrome P-450 dependent benzo(a)pyrene hydroxylase activity by acetylenic and olefinic polycyclic arylhydrocarbons

Thesis/Dissertation · Wed Jan 01 00:00:00 EST 1986

OSTI ID:6543960

Gan, L S

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
• Resource Relation: Other Information: Thesis (Ph. D)
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
59 BASIC BIOLOGICAL SCIENCES
ACETYLENE
MUTAGEN SCREENING
TOXICITY
ALKENES
HYDROXYLASES
ENZYME ACTIVITY
COVALENCE
HAMSTERS
LIVER
LUNGS
MICROSOMES
RATS
STOICHIOMETRY
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ALKYNES
ANIMALS
BODY
CELL CONSTITUENTS
DIGESTIVE SYSTEM
ENZYMES
GLANDS
HYDROCARBONS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
ORGANIC COMPOUNDS
ORGANOIDS
ORGANS
OXIDOREDUCTASES
RESPIRATORY SYSTEM
RODENTS
SCREENING
VERTEBRATES
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550501 - Metabolism- Tracer Techniques