Dose and dose-rate effects of X rays and fission neutrons on lymphocyte apoptosis in p53(+/+) and p53(-/-) mice
Dose and dose-rate effects of X rays and fission neutrons on lymphocyte apoptosis in p53(+/+) and p53(-/-) mice
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DOI：
10.1269/jrr.41.113
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发表时间：
2000-06-01
影响因子：
2
通讯作者：
Kondo, S
中科院分区：
文献类型：
--
作者：
Fujikawa, K;Hasegawa, Y;Kondo, S
将小鼠暴露于X射线或裂变中子后，4小时后测量细胞凋亡频率（F），24小时后测量胸腺和脾脏中的体重减轻或淋巴细胞含量损失。在p53(+/+)小鼠中，F随剂量(D(Gy))线性增加，X射线和裂变中子每Gy的F诱导率(通过TUNEL染色检测)分别为0.05和0.23。因此，诱导细胞凋亡的裂变中子的RBE为4.6。这表明辐射诱导的细胞凋亡主要是由于DNA中的双链断裂（DSB），因为我们之前获得了几乎相同的裂变中子的RBE值，用于诱导果蝇中的交叉突变，这是由DSB的重组修复引起的。在p53(+/+)小鼠中，X射线照射24小时后观察到胸腺和脾脏的器官重量和淋巴细胞含量下降。胸腺和脾脏中的这些萎缩变化在数量上与它们中发生的凋亡细胞死亡总数相对应。然而，在p53(-/-)小鼠中，X射线照射后没有诱导剧烈的细胞凋亡，并且在X射线照射后24小时，胸腺和脾脏中出现体重和淋巴细胞含量的增生性变化。在 p53(+/+) 小鼠中，急性 (0.4 Gy/min) 和慢性 (3 mGy/min) 伽玛射线照射之间每 Gy 诱导的淋巴细胞存活分数减少率没有差异。即，辐射诱导的淋巴细胞凋亡是剂量率独立事件。
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.