RADIOSENSITIVE POPULATIONS AND RECOVERY IN X-RAY-INDUCED APOPTOSIS INTHE DEVELOPING CEREBELLUM

Sprague-Dawley rats received a single dose of 2 Gy X-rays at the age o f 1 or 3 days and were killed at different intervals. Dying cells with the morphological characteristics of apoptosis appeared in the extern al and internal granular layers (EGL and IGL) and white matter (WM) of the cerebellum, mainly 3-6 h after irradiation, and decreased thereaf ter to reach normal values between 48 h and 5 days later. This process was curbed by the injection of cycloheximide at a dose of 1 mug/g bod y weight. In addition, the number of mitoses in EGL rapidly decreased after irradiation and did not reach normal values until a few days lat er. Proliferating cell nuclear antigen (PCNA)-immunoreactive cells, wh ich were chiefly found in EGL but also in IGL and WM, dramatically dec reased in number from 3 to 48 h after irradiation. PCNA-immunoreactive cells reappeared and reached age-matched values in the following days . Hu (considered as an early neuronal marker) and vimentin immunocytoc hemistry disclosed that Hu-nonreactive cells in the upper level of EGL , Hu-immunoreactive cells in the inner level of EGL, Bergmann glia and many astrocytes in WM, as well as many non-typified cells in WM, were radiosensitive populations, whereas Purkinje cells were not. The pres ent results indicate that irradiation at Pl or P3 blocks mitosis in EG L and kills sensitive cells mainly in the late G1 and S phases of the cell cycle, probably by apoptosis through a protein synthesis-mediated process. Radiosensitive cells are germinal cells and neuroblasts in E GL, Bergmann glia, astrocytes in WM, and non-typified cells, probably glial cell precursors, in WM. Surviving cells in EGL and PCNA-immunore active cells in other cortical layers and white matter reconstitute th e cerebellum following a single dose of X-rays.