Effect of In Utero Irradiation on the Postnatal Development, Behavior, and Brain Structure of Rats: Dose Fractionation with a 6-h Interval

Based on previous studies showing that exposure of the rat fetus to ionizing radiation produces dose-dependent (0.25-1.25 Gy) changes in postnatal development of behavior and decreases in the thickness of the cerebral cortex, we examined the extent to which dose fractionation would reduce expression of damage. Pregnant rats were exposed to single doses of 0.5 or 1.0 Gy, or to two doses of 0.5 Gy 6 h apart on day 15 of gestation. Offspring were subjected to four behavioral tests on postnatal days 7-28; the rats were then sacrificed and their brains removed and processed for histology. For all end points, the fractionated dose produced an effect that was intermediate between that of the 0.5- and 1.0-Gy doses and which, by interpolation, could be expressed as equivalent to a single dose between 0.5 and 1.0 Gy. The equivalent single dose was not significantly different from the 1.0-Gy dose for negative geotaxis (0.54 Gy), reflex suspension (0.80 Gy), and continuous corridor (0.85 Gy). For sine of the angle of the advance of hind feet (0.58 Gy), width of stride (0.69 Gy), length of stride (0.75 Gy), body weight (0.73 Gy), and cerebral cortex thickness (0.69 Gy), the fractionated dose produced effects significantly different (P < 0.05) from the 1.0-Gy dose. Overall, exposure of fetal rats to two doses of 0.5 Gy separated by 6 h produced effects equivalent to a single dose of 0.70 Gy, as measured by postnatal behavioral tests and morphological assessment of brain structure.