Dose and dose-rate effects of X rays and fission neutrons on lymphocyte apoptosis in p53(+/+) and p53(-/-) mice.

Following the exposure of mice to X rays or fission neutrons, the frequency (F) of apoptosis was measured after 4 h, and the weight loss or lymphocyte content loss in the thymus and spleen was measured after 24 h. In p53(+/+) mice, F increased linearly with the dose (D (Gy)) and the induced rate per Gy of F (detected by TUNEL staining) was 0.05 and 0.23 for X rays and fission neutrons, respectively. Therefore, the RBE of fission neutrons was 4.6 for apoptosis induction. This indicates that radiation-induced apoptosis is mostly due to double strand breaks (DSBs) in DNA because we previously obtained almost the same RBE value of fission neutrons for the induction of crossover mutations in Drosophila melanogaster, which arise from the recombinational repair of DSBs. In p53(+/+) mice, decreases in the organ weight and the lymphocyte content were observed for the thymus and the spleen 24 h after X-irradiation. These atrophic changes in the thymus and the spleen quantitatively corresponded to the total apoptotic cell deaths occurring in them. However, in p53(-/-) mice, no vigorous apoptosis was induced after X-irradiation, and hyperplastic changes in the weight and the lymphocyte content appeared in the thymus and the spleen 24 h after X-irradiation. In p53(+/+) mice, there was no difference in the induced rate per Gy of reduction in the surviving fraction of lymphocytes between acute (0.4 Gy/min) and chronic (3 mGy/min) gamma-irradiations. Namely, radiation-induced apoptosis in lymphocytes is a dose-rate independent event.