High susceptibility of mouse newborns to delayed appearance of DNA double-strand breaks in neural stem/progenitor cells exposed to ionizing radiation

Fetal brains are known to be extremely sensitive to ionizing radiation, which can induce structural and functional defects in the developing brain. However, there is less data on the effects of radiation on newborn brains. To determine the radiation sensitivity in newborn brains, we determined the number of DNA double-strand breaks (DSBs) appearing at later stage post-irradiation in neural stem/progenitor cells (NSPCs) of mouse newborns <3 days old, and compared it with the numbers of DSBs of fetal, 1-week-neonate, 2-week-neonate, and adult mice. DSBs in the nucleus were quantified by counting the number of foci of phosphorylated histone H2AX (gamma-H2AX) in NPSCs using a newly developed computer program. Then, we irradiated 14-day fetuses, newborns <3 days old, 1-week-old neonates, 2-week-old neonates, and 12-week-old adult mice with 2 Gy of X-rays. At 6-7 weeks post-irradiation, the brain tissues isolated from the mice were incubated, and DSBs in the growing neurospheres were counted using a focus-counting program. The delayed appearance of DSBs by X-irradiation was evident in NSPCs derived from newborns <3 days old, as well as in 1-week-old neonates, 2-week-old neonates and adult mice, but not 14-day fetuses, at 6-7 weeks post-irradiation. It was of particular interest that the NSPCs of newborns were 2.5-fold more susceptible than those of adults to radiation-induced delayed appearance of DSBs, indicating that newborns <3 days old are the most vulnerable to the delayed effects of radiation among the mouse groups examined.