TI - Radiation response of neural precursor cells : linking cellular sensitivity to cell cycle checkpoints , apoptosis and oxidative stress . AB - Therapeutic irradiation of the brain can cause a progressive cognitive dysfunction that may involve defects in neurogenesis . In an effort to understand the mechanisms underlying radiation-induced stem cell dysfunction , neural precursor cells isolated from the adult rat hippocampus were analyzed for acute ( 0-24 h ) and chronic ( 3-33 days ) changes in apoptosis and reactive oxygen species ( ROS ) after exposure to X rays . Irradiated neural precursor cells exhibited an acute dose -dependent apoptosis accompanied by an increase in ROS that persisted over a 3-4-week period . The radiation effects included the activation of cell cycle checkpoints that were associated with increased Trp53 phosphorylation and Trp53 and p21 ( Cdkn1a ) protein levels . In vivo , neural precursor cells within the hippocampal dentate subgranular zone exhibited significant sensitivity to radiation . Proliferating precursor cells and their progeny ( i.e. immature neurons ) exhibited dose -dependent reductions in cell number . These reductions were less severe in Trp53-null mice , possibly due to the disruption of apoptosis . These data suggest that the apoptotic and ROS responses may be tied to Trp53 -dependent regulation of cell cycle control and stress-activated pathways . The temporal coincidence between in vitro and in vivo measurements of apoptosis suggests that oxidative stress may provide a mechanistic explanation for radiation-induced inhibition of neurogenesis in the development of cognitive impairment .