Comparison of tumour susceptibility among various organs of foetal, young and adult ICR/Jcl mice.

Urethane was found to be uniformly distributed in all the major organs of foetal, young and adult ICR/Jcl mice and then to disappear rapidly as measured by the incorporation of urethane-carbonyl-14C, thus permitting the accurate comparison of tumour susceptibility of cells in various organs of mice at different ages. Lung tumour frequency (tumours/lung) was significantly higher in mice treated with urethane when young (21 days old) and adult (63 days old) than in those treated in utero (Days 11-19 of gestation). When relative sensitivity of a lung cell was calculated as the ratio of average number of tumours per lung per mg of lung at the time of treatment, however, a lung cell of the foetus was more sensitive to urethane than that of the young and adult. Hepatomata were induced significantly only when male foetuses and neonates were exposed to urethane. The offspring exposed to urethane on Days 11-16, however, developed hepatomata in lower incidence than those exposed on Days 14-19, whereas the previous investigation by the author revealed that Days 11-13 correspond to the stage most sensitive to hepatocarcinogenesis. This contradiction was due to the occurrence of testicular hypogenesis (chemical castration) in all offspring of the former group. Differentiating female gonad and rapidly proliferating blood vessels of the placenta and deciduum were also sensitive to tumour induction by urethane. Thus, high tumour susceptibility of rapidly proliferating and undifferentiated cells suggests that some initiating events in the process of carcinogenesis may occur during or after DNA replication. Leukaemia induction in the young mice, but not in the foetus, remains to be elucidated.