Pregnant ICR mice were treated with single whole-body X-radiation at a dose of 0.24 Gy on day 10, 13, or 15 of gestation. Fetuses were obtained from mothers during 1 and 24 hours after irradiation. Pyknotic cells in the ventricular zone of telencephalon were counted in serial histological sections. Incidence of pyknotic cells peaked during 6 and 9 hours after irradiation in each gestation day group. Then, dose-response curves were obtained 6 hours after 0-0.48 Gy of irradiation. All three dose-response curves showed clear linearity in the dose range lower than 0.24 Gy. Ratios of radiosensitivity estimated from the slopes of dose-response curves in day 10, 13, and 15 groups were 1, 1.4, and 0.4, respectively. These demonstrated that ventricular cells in the day 13 fetal telencephalon were the most radiosensitive among the three different age groups. In order to confirm the presence of the highly radiosensitive stage common to mammalian cerebral cortical histogenesis, pregnant F344 rats were treated with single whole-body gamma-irradiation at a dose of 0.48 Gy on day 13, 14, 15, 17, or 19 of gestation. The incidence of pyknotic cells in the ventricular zone of telencephalon was examined microscopically during 1 and 24 hours after irradiation. The peak incidence was shown 6 hours after irradiation in all the treated groups, and the highest peak incidence was shown in day-15-treated group. The developmental stage of telencephalon of day 15 rat fetuses was comparable to that of day 13 mouse fetuses. Thus, the highest radiosensitivity in terms of acute cell death was shown in the same developmental stage of brain development, i.e., the beginning phase of cerebral cortical histogenesis, in both mice and rats.
Effects of cycloheximide and actinomycin D on radiation-induced cell death in the external granular layer (EGL) of the cerebellum were studied in vivo. Newborn mice were exposed to 0.24 Gy gamma-radiation, and dying cells which exhibited pyknosis of nuclei in the EGL were examined at various post-irradiation periods. The number of pyknotic cells began to increase 3 h after irradiation, reached a peak incidence at 6 h, and then gradually fell to the sham-irradiated level by 18 h. When pups were injected with cycloheximide 1 h after irradiation, cell death was suppressed for 6 h, but a peak mortality as high as in the case of radiation alone was attained at 15 h after irradiation. When pups were treated with cycloheximide twice, at 1 and 6 h after irradiation, cell death did not occur for 15 h, but then the incidence rose to a level similar to that after irradiation alone. These findings showed that radiation-induced cell death in the EGL is suppressed by cycloheximide until the chemical is metabolized. Hence, death is by apoptosis which is known to require macromolecular synthesis, and the 'signal' for apoptosis in the cell persists for at least 15 h after irradiation. On the other hand, actinomycin D injected immediately before or after irradiation did not affect the initiation of cell death; actinomycin D alone induced cell death.
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