DISTRIBUTION AND METABOLISM OF 1-PROPYL-1-NITROSOUREA IN RATS

Abstract

The carcinogen 1-[14C]propyl-1-nitrosourea (PNU) was readily absorbed from the rat gut, and the radioactivity was excreted mainly in the urine and expired air. The urinary metabolites of PNU were 1-propylurea and urea. 1-Propylurea was excreted largely unchanged in the urine. Both [14C]PNU and 1-[14C]propylurea were eliminated rapidly from the rat body. Besides CO2 from PNU, isopropyl alcohol was identified as a volatile metabolite in the expired air. Specific high concentrations (%/g) in main organs and tissues were not observed in adult rats 24 h after single p.o. doses (20 mg/kg) of labeled PNU. The ureido carbon of PNU showed considerable retention in the blood, while relatively high residual levels were found in the liver for the propyl carbon. Autoradiographic studies on pregnant rats showed a uniform distribution between maternal and fetal bodies a short time after dosing. A relatively high concentration of 14C label was found in the maternal blood 24 h after treatment with [carbonyl-14C]PNU. Localization of radioactivity in bone systems such as the fetal sterna and vertebrae was noted 6 h after treatment with [propyl-1-14C]PNU. Metabolic pathways of PNU in the rat are proposed.