Excretion and metabolism of 1-nitropyrene in rats after oral or intraperitoneal administration.
Many nitro-substituted polycyclic aromatic hydrocarbons (NPAHs) have been identified as environmental pollutants and have been found to be mutagens and carcinogens in bacteria and mammalian systems. They require metabolism to express their biological activity. The metabolism and excretion of 1-nitropyrene (NP), a prevalent NPAH, by Fischer-344 rats after intraperitoneal (ip) or oral administration was studied. Radiolabeled NP was administered to rats (10 mg NP/kg body wt), and urine and feces were collected for 7 days. After ip administration of [14C]NP, 60% of the radioactivity was found in the urine and 20% in the feces. Likewise, 55 and 35% of the orally administered 14C was found in urine and feces, respectively. Both urine and feces were analyzed by high-pressure liquid chromatography for metabolites. The majority of the radioactivity in both urine and feces was associated with very polar metabolites, none accounting for more than 10% of the dose. Small amounts (less than 1% of the dose) of aminopyrene (AP), acetylaminopyrene, and NP were detected. A urinary metabolite (3-8% of the dose) was found that converted to acetylaminopyrene phenol (two isomers) when urine was heated overnight at 37 degrees C at pH 4.5. More of this metabolite (2.2 times) as well as AP (1.8 times), was excreted after oral than after ip administration of NP. The NP metabolites found in this study demonstrate that reduction of the nitro group is a significant route of NP metabolism in rats. Since nitroreduction appears to be necessary in the activation of NPAHs to bacterial mutagens, this indicates that similar metabolic pathways are present in rats (catalyzed by mammalian and/or gut bacterial enzymes) and that activation of NPAHs to carcinogens or toxins by nitroreduction is possible.
D000284:Administration, Oral; D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D005243:Feces / Q000032:analysis; D005260:Female; D005965:Glucuronates / Q000378:metabolism; D007274:Injections, Intraperitoneal; D009682:Magnetic Resonance Spectroscopy; D011721:Pyrenes / Q000008:administration & dosage / Q000378:metabolism* / Q000652:urine; D051381:Rats; D011916:Rats, Inbred F344; D013431:Sulfates / Q000378:metabolism; D013997:Time Factors
D005965:Glucuronates; D011721:Pyrenes; D013431:Sulfates; C032668:1-nitropyrene