Effects of prenatal treatment with tritiated water on the developing brain in mouse

Pregnant mice were injected intraperitoneally with various doses of tritiated water on embryonic day 13. The litters received total cumulative absorbed beta-irradiation to a dose of 0, 0.1, 0.2, 0.4 or 0.8 Gy. We found that 0.4 Gy beta-irradiation caused a significant reduction in brain weight but not in body weight among 8-week-old mice. The highest dose (0.8 Gy) inhibited both body and brain development. A quantitative study showed that a significant reduction in cerebral pyramidal cells was present in the groups exposed to > or = 0.2 Gy. In tritiated, water-treated groups, the pyramidal cells reduced in a dose-dependent manner, with reductions ranging from 3 to 12%. The thickness of cerebral cortex was significantly reduced in the groups exposed to > or = 0.4 Gy. Numerical density of pyramidal cells was the most sensitive indicator of developmental disturbance of cerebral cortex manifested postnatally. No significant difference in the numerical density of Purkinje cells was found between the irradiated and control groups. These results demonstrated that the time at which the insult occurred was an important factor determining the resulting abnormalities.