Radiation-induced tissue abnormalities in fetal brain are related to apoptosis immediately after irradiation
Radiation-induced tissue abnormalities in fetal brain are related to apoptosis immediately after irradiation
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DOI：
10.1080/095530000138312
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发表时间：
2000-05-01
影响因子：
2.6
通讯作者：
Yoshida, K
中科院分区：
文献类型：
--
作者：
Kubota, Y;Takahashi, S;Yoshida, K
目的：为了探讨辐射诱导的胎脑组织异常的发病率和p53依赖的apoptosis的程度之间的关系，材料和方法：妊娠小鼠与野生型p53（+ / +），杂合型p53（+ / -）和纯合突变型p53（- / -）的胎儿在妊娠第13天接受全身X射线照射。结果：p53（+ / +）和p53（+ / -）胎儿的凋亡细胞百分比随剂量呈线性增加，但p53（-/ -）胎儿的凋亡细胞百分比未发现增加。在p53（+ / -）胎仔中需要大约两倍的剂量才能诱导p53（+ / +）中观察到的凋亡反应。在1.5和3.0戈伊剂量下，出现脑组织异常的胎仔，如脑室衬里破坏和中央空洞的脑嵴，在p53（+ / +）和p53（+ / -）小鼠中，分别在2.25和3.75戈伊剂量下，发生率显著增加。但在3.75Gy剂量下，p53（- / -）未见组织异常。在p53（+ / -）胎儿中大约需要两倍的剂量才能诱导p53（+ / +）小鼠脑组织异常的程度。结论：照射后6小时的凋亡程度与照射后3天脑组织异常的发生率和严重程度相对应，表明照射诱导的组织异常是由辐射引起的。如心室内膜破坏、神经胶质纤维紊乱、脑内神经元出现等，与照射后6小时出现的细胞凋亡密切相关。
Purpose: To investigate the relation between the incidence of radiation-induced tissue abnormalities in fetal brain and the extent of p53-dependent apoptosis.Materials and Methods: Pregnant mice with wild-type p53(+ / +), heterozygous p53(+ / -) and homozygous mutant p53(- / -) fetuses received whole-body X-irradiation on day 13 of gestation. The extent of apoptosis 6 hr after irradiation and the incidence of tissue abnormalities 3 days after irradiation in the brain were evaluated by histological examination of brain mantle.Results: The percentage of apoptotic cells increased linearly with dose in p53(+ / +) and p53(+ / -)fetuses, but no increase was found in p53(-/ -). Approximately twice the dose was necessary in p53(+ / -) fetuses to induce an apoptotic response to the extent observed in p53(+ / +). Fetuses with brain-tissue abnormalities, such as a destroyed ventricular lining and rosettes with a central hollow appeared at a dose of 1.5 and 3.0 Gy, and the incidence was markedly increased following a dose of 2.25 and 3.75 Gy in p53(+ / +) and p53(+ / -) mice, respectively, but no fetus with tissue abnormalities appeared in p53(- / -) at up to 3.75Gy. Approximately twice the dose was necessary in p53(+ / -) fetuses to induce brain-tissue abnormalities to the extent seen in p53(+ / +)mice.Conclusion: The extent of apoptosis 6 hr after irradiation and the incidence and severity of brain-tissue abnormalities 3 days after irradiation corresponded well, suggesting that radiation-induced tissue abnormalities! such as destroyed ventricular lining, deranged glial fibre and appearance of rosettes in fetal brain were closely related to apoptosis seen 6 hr after irradiation.