Induction of tumors by direct injection of N-ethyl-N-nitrosourea into the amniotic space of the mouse fetus.

An N-ethyl-N-nitrosourea (ENU) solution was injected into the amniotic space of Swiss mouse fetuses. Embryos 9 days old were exposed to 2 and 4 micrograms ENU and died within the first 4 weeks of life. Injection of 4 micrograms ENU into 11-day-old fetuses induced a 10% lung tumor incidence, whereas 16 micrograms injected at 12, 15, or 16 days resulted in lung tumor incidences of 42, 100, and 84%, respectively. A mortality rate of 50% and a lung tumor incidence of 89% in survivors resulted after exposure of 16-day-old fetuses to 64 micrograms ENU. Histologic examination revealed that the tumors were alveologenic adenomas 1--7 mm in diameter. Two saline-treated control groups had no tumors. The possible utilization of this biologic model in testing chemical alkylating agents similar to ENU is discussed.