Metabolism of benzo(a)pyrene and (-)-trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene by rat liver nuclei and microsomes

Journal Article · Mon May 01 04:00:00 EDT 1978 · Cancer Res.; (United States)

OSTI ID:6789428

Pezzuto, J M; Yang, C S; Yang, S K; McCourt, D W; Gelboin, H V

The metabolism of benzo(a)pyrene and (-)-trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene was examined by high-pressure liquid chromatography. Liver nuclei or microsomes from control, 3-methylcholanthrene-treated, or phenobarbital-treated rats were used. An improved method of separating the metabolites is described. Upon treatment with 3-methylcholanthrene, metabolism of benzo(a)pyrene was enhanced 4- and 9-fold in microsomes and nuclei, respectively. No enhancement was observed with phenobarbital treatment. The pattern of metabolites obtained with nuclei was similar to that of the corresponding microsomes, although quantitatively reduced. Nuclei and microsomes also metabolized (-)-trans--7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene to 7,8-diol-9,10-epoxides and again the metabolic pattern was similar. Each of the nuclear samples produced less diol-epoxides than did the corresponding microsomes. Treatment with 3-methylcholanthrene caused an 8-fold increase in r-7, t-8-dihydroxy-t-9, 10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene (diol-epoxide 1) formation with microsomes but only a 2-fold increase with nuclei. Inducible, r-7, t-8-dihydroxy-c-9, 10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene (diol-epoxide II) formation was also detected. Phenobarbital treatment did not greatly increase diol-epoxide formation. Since both the microsomes and the nuclei can produce diol-epoxides, both organelles may be considered as potentially important sites of carcinogen activation.

• Research Organization: New Jersey Medical School, Newark
• OSTI ID: 6789428
• Journal Information: Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 38:5; ISSN CNREA
• Country of Publication: United States
• Language: English

Related Subjects

550600 -- Medicine
550900* -- Pathology
59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
ALCOHOLS
ANIMALS
AROMATICS
AZINES
BARBITURATES
BENZOPYRENE
BODY
CARCINOGENESIS
CELL CONSTITUENTS
CELL NUCLEI
CHEMICAL ACTIVATION
CONDENSED AROMATICS
DIGESTIVE SYSTEM
DRUGS
EPOXIDES
GLANDS
GLYCOLS
HETEROCYCLIC COMPOUNDS
HYDROCARBONS
HYDROXY COMPOUNDS
HYPNOTICS AND SEDATIVES
LIVER
MAMMALS
MEDICINE
METABOLISM
METABOLITES
MICROSOMES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANOIDS
ORGANS
PATHOGENESIS
PHENOBARBITAL
POLYCYCLIC AROMATIC HYDROCARBONS
PYRIMIDINES
RATS
RODENTS
VERTEBRATES