Regio- and stereoselectivity of various forms of purified cytochrome P-450 in the metabolism of benzo(a)pyrene and (-)trans-7-8-dihydroxy-7-8-dihydrobenzo(a)pyrene as shown by product formation and binding to DNA

Journal Article · Sat Jul 01 04:00:00 EDT 1978 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.75.7.3123· OSTI ID:6470950

Deutsch, J ^[1]; Leutz, J C; Yang, S K; Gelboin, H V; Chiang, Y L; Vatsis, K P; Coon, M J

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1. National Cancer Inst., Bethesda, MD

Highly purified cytochromes P-450(LM2) and P-450/sub LM4) and partially purified P-450(LM1), P-450(sub LM3b), and P-450(LM7) from rabbbit liver microsomes exhibit different catalytic activities in the metabolism of benzol(a)pyrene (BzP) and (-)trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene((-)trnas-7,8-diol) in a reconstituted enzyme system. The two highly purified cytochromes also exhibit differences in the activation of BzP and (-)trans-7,8-diol to intermediates that bind to DNA, as well as in the steroselective conversion of (-)trans-7,8-diol to the highly mutagenic and carcinogenic diol-epoxides r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene (diol-epoxide I) and r-7,t-8-dihydrocy-c-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene (diol-epoxide II). P-450(LM2) is more active than P-450(LM4) in the metabolism of BzP and in its conversion to products that bind to DNA. In contrast, P-450(LM4) is more active than P-450(LM2) in the metabolism of (-)trans-7,8-diol and in its conversion to products that bind to DNA.

• OSTI ID: 6470950
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 75:7; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACTIVATION ANALYSIS
ALCOHOLS
ANIMALS
AROMATICS
BENZOPYRENE
BINDING ENERGY
BIOCHEMISTRY
BODY
CARCINOGENS
CELL CONSTITUENTS
CHARGED-PARTICLE ACTIVATION
CHEMISTRY
CONDENSED AROMATICS
CYTOCHROMES
DIGESTIVE SYSTEM
DNA
ENERGY
ENZYMES
GLANDS
GLYCOLS
HYDROCARBONS
HYDROXY COMPOUNDS
LIVER
MAMMALS
METABOLISM
MICROSOMES
MUTAGENS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANOIDS
ORGANS
PHOTON ACTIVATION ANALYSIS
PIGMENTS
RABBITS
STEREOCHEMISTRY
VERTEBRATES