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 00:00:00 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), Vol. 75:7
• Country of Publication: United States
• Language: English

Related Subjects

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