Metabolism of 1-Nitro[a-4,5,9,10-14C]pyrene in the F344 Rat

Karam El-Bayoumy, Stephen S. Hecht

Research output: Contribution to journalArticle

57 Citations (Scopus)

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 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-ni-tro-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-hydroxy-pyrene 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.

Original languageEnglish (US)
Pages (from-to)4317-4322
Number of pages6
JournalCancer Research
Volume44
Issue number10
StatePublished - Oct 1 1984

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1-nitropyrene
Inbred F344 Rats
Bile
Urine
Glucuronides
Sulfates
Feces
Carcinogenesis
Body Weight
pyrene
1-hydroxypyrene
Water
1-aminopyrene

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

El-Bayoumy, Karam ; Hecht, Stephen S. / Metabolism of 1-Nitro[a-4,5,9,10-14C]pyrene in the F344 Rat. In: Cancer Research. 1984 ; Vol. 44, No. 10. pp. 4317-4322.
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title = "Metabolism of 1-Nitro[a-4,5,9,10-14C]pyrene in the F344 Rat",
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 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-ni-tro-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-hydroxy-pyrene 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.",
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Metabolism of 1-Nitro[a-4,5,9,10-14C]pyrene in the F344 Rat. / El-Bayoumy, Karam; Hecht, Stephen S.

In: Cancer Research, Vol. 44, No. 10, 01.10.1984, p. 4317-4322.

Research output: Contribution to journalArticle

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