Studies on the distribution and metabolism of N-[14C]nitrosopyrrolidine in mice.
Pretreatments with pyrazole, ethanol, nialamide or diethyldithiocarbamate were found to strongly depress the exhalation of 14CO2 and the incorporation of radioactivity in the acid-insoluble fraction of the liver in mice injected with N-[14C]nitrosopyrrolidine. Whole-body autoradiography performed with hemisections of mice at -80 degrees C (to prevent evaporation of the volatile N-nitrosopyrrolidine) and with dry tape-sections (to localize the non-volatile metabolites), using pretreated and non-pretreated mice, indicated a uniform distribution of the non-metabolized N-nitrosopyrrolidine in the tissues. At the shortest survival intervals (1 and 5 min), a high level of metabolites were found in the liver, the tracheo-bronchial and nasal mucosa and Harder's gland, indicating a local formation of metabolits in these tissues. At later survival intervals (0.5--24 h) metabolites were in addition found in tissues with a rapid cell turnover and a high rate of protein synthesis and in brown fat, which probably reflects incorporation of metabolites via normal biosynthetic pathways. Autoradiography of N-[14C]nitrosopyrrolidine in mice given the substance orally resulted in distribution pictures similar to those obtained after i.v. injections.
D000818:Animals; D001345:Autoradiography; D002245:Carbon Dioxide; D002250:Carbon Radioisotopes; D000431:Ethanol / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009242:N-Nitrosopyrrolidine / Q000378:metabolism*; D009526:Nialamide / Q000494:pharmacology; D009602:Nitrosamines / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D009602:Nitrosamines; D011720:Pyrazoles; D013859:Thiocarbamates; D002245:Carbon Dioxide; D000431:Ethanol; D009242:N-Nitrosopyrrolidine; D009526:Nialamide