The effects of X-irradiation, N-ethyl-N-nitrosourea or combined treatment on O6-alkylguanine-DNA alkyltransferase activity in fetal rat brain and liver and the induction of CNS tumours.

Wistar rats were treated in utero on day 16 of gestation either by X-irradiation (1 and 2 Gy), N-ethyl-N-nitrosourea (ENU, 50 mg/kg), or both in combination. The O6-alkylguanine-DNA alkyltransferase (AT) activity of the fetal brain and liver was analyzed and long-term observations were made to reveal any relationship between the O6-ethylguanine repair capability and tumour incidence in the organs of the offspring. The AT activity in the brain was affected to the same extent in the fetuses as in the dams. There was a 60.9% decrease in AT activity in fetuses 24 h after ENU treatment. This correlates with a significant increase in the incidence of brain tumours in the treated offspring (44.1%) compared to control animals. The inductive effect of X-irradiation on AT activity (131.3% for 1 Gy and 201.6% for 2 Gy) corresponded in turn with a reduction of the incidence of tumours after the combined treatment (26.8% and 8.3% tumour incidence, 103.1% and 157.8% AT activity). In the liver of the rat fetuses, there was generally no effect of treatment on AT activity in contrast to the results obtained for the dams, where an increased AT activity (127.70% and 157.4% after X-irradiation, 149.0% and 156.1% after combined treatment) was observed. There were no tumours of the liver observed in the offspring after either treatment alone or after combined treatment. Comparing biochemical and morphological results, it is suggested that X-irradiation of rat fetuses--with relatively low doses--and subsequent treatment with the ethylating carcinogen ENU, could significantly reduce the incidence of brain tumours in adult life. This is possibly a result of the corresponding induction of AT.