This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by El-Bayoumy, K. Articles by Hecht, S. S. Search for Related Content PubMed PubMed Citation Articles by El-Bayoumy, K. Articles by Hecht, S. S.

Metabolism of 1-Nitro[U-4,5,9,10-¹⁴C]pyrene in the F344 Rat¹

Division of Chemical Carcinogenesis, Section of Biological Chemistry, Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, New York 10595

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.

¹ This study was supported by National Cancer Institute Grant CA-35519. Presented at the 74th Annual Meeting of the American Association for Cancer Research, San Diego, CA, 1983 (4). This is Paper 69 of the series, "A Study of Chemical Carcinogenesis."

² To whom requests for reprints should be addressed.

Received 1/26/84. Accepted 6/22/84.

This article has been cited by other articles:

				Y.-H. Chae, T. Thomas, F. P. Guengerich, P. P. Fu, and K. El-Bayoumy Comparative Metabolism of 1-, 2-, and 4-Nitropyrene by Human Hepatic and Pulmonary Microsomes Cancer Res., April 1, 1999; 59(7): 1473 - 1480. [Abstract] [Full Text] [PDF]