Metabolism of 1-propyl-1-nitrosourea (PNU) in rats

The carcinogen, 14C-1-propyl-1-nitrosourea (PNU), was found to be 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-propyl-urea (PU) and urea. The metabolite PU was shown to be excreted largely unchanged in the urine. Both 14C-PNU and 14C-PU were found to be eliminated rapidly from the rat body. In addition to CO2 from PNU, isopropanol was identified as a volatile metabolite in breath. Specific, high organ-affinity was not observed in adult rats 24 h after single p.o. doses of 14C-PNU. However, 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 uniform distribution between maternal and fetal bodies a short time after dosing. A relatively high concentration of 14C was found in the maternal blood after 24 h with PNU (carbonyl-14C). Localization of the radioactivity in bone systems, such as fetal sterna and vertebrae, was noticed after 6 h with PNU (propyl-1-14C). Metabolic pathways of PNU are proposed and biochemical aspects of PNU metabolism in rats are discussed.