A STUDY OF CHEMICAL CARCINOGENESIS .69. METABOLISM OF 1-NITRO[U-4,5,9,10-C-14]PYRENE IN THE F344 RAT

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (10) , 4317-4322
Abstract
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 h, 41% of the dose was eliminated in the feces and 16% was eliminated in the urine. The corresponding figures after 120 h were 51 and 19%. In rats with bile cannulae, 37% of the dose was excreted in the bile after 72 h 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-aminohydroxpyrenes 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 .apprx. 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. Metabolic reduction of the highly mutagenic 1-nitrohydroxypyrenes does occur in vivo in the rat. This is a possible activation pathway in 1-nitropyrene carcinogenesis. [Implications with respect to the role of 1-nitrohydroxypyrenes as diesel exhaust environmental pollutants are discussed.].

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