Distribution and excretion of 1,8-dinitro[14C]pyrene in the mouse.
The disposition of the environmental pollutant and potent mutagen and carcinogen, 1,8-dinitropyrene (DNP) in female BALB/c mice was investigated. In the first 48 h after oral administration of 1,8-dinitro[4,5,9,10-14C]pyrene ([14C]DNP), 42% of the dose was eliminated in the faeces and 12% in the urine. Faeces was the major pathway of excretion with 45% of the dose being eliminated by this route in 9 days. Distribution of DNP in various tissues (blood, liver, spleen, lungs, kidneys, stomach, small and large intestine) was studied over 9 days. There was a linear increase in the concentration of radioactive material in the blood, liver and kidneys up to 6 h after [14C]DNP administration, representing 0.27, 2.9 and 0.21% of the radioactive dose, respectively. The corresponding figures after 24 h decreased to 0.1, 1.6 and 0.12%, respectively. In comparison, radioactivity present in the spleen and lungs was low and did not significantly change with time. In studies with ligated sections of the gastrointestinal tract, DNP absorption was from the small and large intestine and there was none from the stomach. The rate of absorption of DNP from the small intestine was greater than that from the large intestine, although overall uptake of the compound was poor (more than 80% of the original dose was recovered from the ligated small intestine after 120 min). The data from these studies suggest that although absorption of orally administered DNP is slow, the compound or its metabolites persist in the body for long periods and the liver should be considered as the major target organ.
Shah
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School of Biological Sciences, Portsmouth Polytechnic, U.K.
Rowland
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Combes
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D000284:Administration, Oral; D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000378:metabolism*; D005243:Feces / Q000032:analysis; D005260:Female; D007408:Intestinal Absorption; D051379:Mice; D008807:Mice, Inbred BALB C; D011721:Pyrenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013997:Time Factors; D014018:Tissue Distribution
D002273:Carcinogens; D004785:Environmental Pollutants; D011721:Pyrenes; C033310:1,8-dinitropyrene