Studies on the distribution and metabolism of 14C-dimethylnitrosamine in foetal and young mice.

Abstract

In pregnant mice injected with 14C-dimethylnitrosamine, whole-body autoradiography was performed with hemisections at -80 degrees (to prevent evaporation of the volatile dimethylnitrosamine) and with dry tape sections (to localize the non-volatile metabolites). The results indicated that the non-metabolized substance passed to the foetal tissues with a uniform distribution and without formation or accumulation of non-volatile metabolites. Autoradiography in young (1-10 days old) and adult mice showed a high level of metabolites in the liver already 5 min. after the administration of 14C-dimethylnitrosamine. No metabolism of the substance could be detected at in vitro incubations of liver tissue obtained from foetuses on the last day of gestation (14CO2-production and incorporation of radioactivity in acid-insoluble macromolecules were used as metabolic indices). However, in vitro experiments with livers of 1-5 days old mice indicated a rapid increase in enzymatic activity after birth. Studies in vivo showed an increased incorporation of radioactivity in the acid-insoluble macromolecules of the liver and a decreased exhalation of 14CO2 in 10 and 14 days old mice as compared with 21 and 60 days old mice. This indicates a difference in the fate of dimethylnitrosamine in vivo between the young and older mice.