Benzo(a)pyrene metabolism by murine spleen microsomes

Journal Article · Wed Nov 01 04:00:00 EST 1989 · Cancer Research; (USA)

OSTI ID:5223642

Kawabata, T T; White, Jr, K L ^[1]

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1. Virginia Commonwealth Univ., Richmond (USA)

The immunosuppressive actions of benzo(a)pyrene have been proposed to be mediated by reactive metabolites rather than the parent compound. Reactive metabolites which suppress splenic humoral immune responses are thought to be generated within the spleen rather than in distant tissues. Although the spleen has been shown to be capable of metabolizing benzo(a)pyrene, the relative amounts and types of metabolites generated have not been determined. In this study, high-pressure liquid chromatography was used to separate benzo(a)pyrene metabolites generated by splenic microsomes. The major metabolites generated by the splenic microsomal preparations of untreated female B6C3F1 mice were found to be the 9,10- and 7,8-dihydrodiols and 9-, 7-, and 3-hydroxy benzo(a)pyrene. The 1,3-, 3,6-, and 6,12-diones and 4,5-dihydrodiol constituted only a small fraction of the metabolites generated. The generation of all metabolites were inhibited by alpha-naphthoflavone and antiserum to NADPH-cytochrome P-450 reductase, whereas SKF 525-A had only a minimal effect. Dihydrodiol production was completely inhibited by the epoxide hydrolase inhibitor, trichloropropylene oxide. Benzo(a)pyrene pretreatment of mice produced a dramatic increase in the amount of metabolites formed; however, the pattern of metabolites remained similar to that generated by splenic microsomes of untreated mice. The role of prostaglandin synthetase in generating these metabolites was also examined. The addition of arachidonic acid in place of NADPH resulted in the formation of only quinones. Dihydrodiols and phenols were undetectable. The results of this study indicate that splenocytes may be capable of generating the 7,8-dihydrodiol, the precursor to the highly reactive 7,8-dihydrodiol-9,10-epoxide.

• OSTI ID: 5223642
• Journal Information: Cancer Research; (USA), Journal Name: Cancer Research; (USA) Vol. 49:21; ISSN CNREA; ISSN 0008-5472
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
AROMATICS
BENZOPYRENE
BIOLOGICAL FUNCTIONS
BODY
CELL CONSTITUENTS
CHROMATOGRAPHY
CONDENSED AROMATICS
ENZYME INHIBITORS
ENZYMES
FUNCTIONS
HYDROCARBONS
IMMUNE REACTIONS
LIGASES
LIQUID COLUMN CHROMATOGRAPHY
MAMMALS
METABOLISM
METABOLITES
MICE
MICROSOMES
MIXED-FUNCTION OXIDASES
ORGANIC COMPOUNDS
ORGANOIDS
ORGANS
OXIDOREDUCTASES
OXYGENASES
RIBOSOMES
RODENTS
SEPARATION PROCESSES
SPLEEN
VERTEBRATES