Metabolism of 1-nitro(U-4,5,9,10-14C)pyrene in the F344 rat
1-Nitro(U-4,5,9,10-14C)pyrene was synthesized and administered to male F344 rats by intragastric gavage at a dose of 100 mg/kg of body weight. During the first 48 hr, 41% of the dose was eliminated in the feces, and 16% was eliminated in the urine. The corresponding figures after 120 hr were 51 and 19%. In rats with bile cannulae, 37% of the dose was excreted in the bile after 72 hr, and 6% was excreted in the urine. Fecal metabolites included 1-aminopyrene (isolated amount, 11.7% of the dose), 1-amino-6-hydroxypyrene and 1-amino-8-hydroxypyrene (4.6%), and unchanged 1-nitropyrene (6.6%). 1-Aminopyrene and the 1-aminohydroxypyrenes were identified as their acetyl-derivatives by comparison of their chromatographic retention times, mass spectra, and UV spectra to those of synthetic standards. Biliary metabolites included 1-aminopyrene, 1-amino-6-hydroxypyrene, 1-amino-8-hydroxypyrene, 1-nitro-6(8)-hydroxypyrene, and 1-nitro-3-hydroxypyrene, as well as their glucuronide and sulfate conjugates. The isolated amounts of these metabolites accounted for approximately 5% of the dose. 1-Amino-6-hydroxypyrene and 1-amino-8-hydroxypyrene and their glucuronide and sulfate conjugates were also tentatively identified in the urine and accounted for about 3% of the dose. Significant quantities of unidentified water soluble metabolites were present in the urine and bile. The results of this study indicate that metabolic reduction of the highly mutagenic 1-nitrohydroxypyrenes occurs in vivo in the rat and suggest that this is a possible activation pathway in 1-nitropyrene carcinogenesis.
- Research Organization:
- Division of Chemical Carcinogenesis, Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, New York
- OSTI ID:
- 6446100
- Journal Information:
- Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 44:10; ISSN CNREA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ABSORPTION
ANIMALS
AROMATICS
BILE
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BODY FLUIDS
CLEARANCE
CONDENSED AROMATICS
EXCRETION
FECES
HYDROCARBONS
INTESTINAL ABSORPTION
MAMMALS
MATERIALS
METABOLISM
METABOLITES
NITRO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PYRENE
RATS
RODENTS
UPTAKE
URINE
VERTEBRATES
WASTES