Selective vulnerability to radiation in the hippocampal dentate granule cells

BACKGROUND Radiation therapy is an effective approach in the treatment of highly radiosensitive brain tumors such as germinomas. However, recent studies have reported intellectual disturbances in patients who underwent whole-brain irradiation as children. We detected apoptosis in the infantile murine cerebrum after systemic X-ray irradiation. METHODS Subjects were 100 ICR mice 4 weeks old, of which 90 were systemically exposed to 18 Gy X-rays (0.45 Gy/min); 10 each were decapitated and the cerebrums were removed 1, 3, 6, 9, 12, 18, 24, 48, and 72 hours after irradiation. Controls were 10 unirradiated mice. DNA fragmentation analysis was carried out by agarose gel electrophoresis, and morphological analysis was by the TUNEL method. RESULTS According to agarose gel electrophoresis, the cerebral DNA ladders were detected only over 6 to 24 hr, peaking in 9 hr. Even at the peak, band intensity was nearly double that of the unirradiated normal thymus. According to the TUNEL analysis, radiation-induced apoptosis increased, with a peak at 9 hours, but decreased 24 hours after irradiation. Apoptotic cells were always localized exclusively in the hippocampal dentate granule cells. CONCLUSIONS We found that vulnerability to radiation existed in the hippocampal dentate granule cells. Intellectual disturbances in patients who have undergone whole-brain irradiation may be caused by injury to the hippocampus. (C) 2000 by Elsevier Science Inc.