Postnatal development and neoplastic disease pattern in NMRI mice after combined treatment with ethylnitrosourea and X-irradiation on different days of the fetal period.

Mice were X-irradiated on day 14, 15 or 16 of gestation with 1·0 Gy. This did not result in an increased tumour frequency in the offspring until 12 months. Mice treated with ethylnitrosourea (ENU) (45 mg/kg) on these gestation days developed a significantly increased tumour frequency in the lungs and liver, and in the ovaries after treatment on day 15 of gestation. Additionally this experiment was the first to show that ENU treatment on gestation day 14, 15 or 16 results in haemangiosarcomas of the subcutis at a low incidence (2·0, 2·4, 2·6 per cent). After combined treatment with these two agents in the sequence X + ENU and an interval of 4 h, a significantly increased incidence rate of animals with tumours was observed in the offspring treated on gestation day 14 or 16. Moreover, the treatment on gestation day 16 exhibited the highest tumour frequency per examined animal (5·7) of all treatment groups. This result is due to a relatively uniform increase of all tumor types. Within this pattern, the frequency of liver tumours was most marked. The diagnosed liver tumours were significantly augmented after X + ENU treatment on day 16. In the reverse sequence (ENU + X), the total tumour outcome was not significantly altered compared with the effects of ENU alone. However, detailed analysis also showed a significant augmentation of the liver tumour frequency with treatment on day 15