Comparison of the in vitro and in vivo hepatic metabolism of the carcinogen 1-nitropyrene

Journal Article · Fri Feb 01 04:00:00 EST 1985 · Carcinogenesis (N.Y.); (United States)

DOI:https://doi.org/10.1093/carcin/6.2.243· OSTI ID:5478627

Howard, P C; Flammang, T J; Beland, F A

(4,5,9,10(-/sup 3/)H)1-nitropyrene was incubated with NADH- or NADPH-fortified rat liver microsomes under an argon atmosphere. Residual substrate and metabolites were extracted with ethyl acetate and analyzed by high pressure liquid chromatography. Both reduced and oxidized products were formed: namely, 1-aminopyrene, trans-4,5-dihydroxy-4,5-dihydro-1-nitropyrene, and 3-, 6- and 8-hydroxy-1-nitropyrene. When incubations were conducted with rat liver cytosol, only the reduced products 1-nitrosopyrene and 1-aminopyrene were detected. In parallel experiments, (4,5, 9,10-/sup 3/H)1-nitropyrene was administered to rats by intravenous injection or gavage and the bile was collected. After 4 h, approximately one-third of the intravenously-administered compound appeared in the bile as O-glucuronides of 3-, 6- and 8-hydroxy-1-nitropyrene, the O-glucuronide of trans-4,5-dihydroxy-4,5-dihydro-1-nitropyrene, and unidentified glutathione conjugates. The same metabolites were found in rats treated with 1-nitropyrene by gavage; however, only 10% of the dose appeared in the bile within 12 h. These studies indicate that both nitroreduction and ring oxidation are involved in the hepatic metabolism of 1-nitropyrene. The importance of these pathways in the etiology of 1-nitropyrene tumorigenesis is discussed.

• Research Organization: National Center for Toxicological Research, Jefferson, AR
• OSTI ID: 5478627
• Journal Information: Carcinogenesis (N.Y.); (United States), Journal Name: Carcinogenesis (N.Y.); (United States) Vol. 6:2; ISSN CRNGD
• Country of Publication: United States
• Language: English

Related Subjects

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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALDEHYDES
AMINES
ANIMALS
BILE
BIOLOGICAL MATERIALS
BODY FLUIDS
CARBOXYLIC ACIDS
CARCINOGENS
CHROMATOGRAPHY
DRUGS
GLUCURONIC ACID
GLUTATHIONE
HYDROXY ACIDS
IN VITRO
IN VIVO
INJECTION
INTAKE
INTRAVENOUS INJECTION
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIQUID COLUMN CHROMATOGRAPHY
MAMMALS
MATERIALS
METABOLIC ACTIVATION
METABOLISM
METABOLITES
NITRO COMPOUNDS
ORAL ADMINISTRATION
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PEPTIDES
POLYCYCLIC AROMATIC AMINES
POLYCYCLIC NITRO COMPOUNDS
POLYPEPTIDES
PROTEINS
RADIOPROTECTIVE SUBSTANCES
RATS
RODENTS
SEPARATION PROCESSES
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES