Nomoto S, Ootsuyama A, Shioyama Y, Katsuki M, Kondo S, Norimura T
Department of Radiation Biology and Health, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Int J Radiat Biol. 1998 Oct;74(4):419-29. doi: 10.1080/095530098141285.
To investigate the relationship between the incidence of radiation-induced malformations and the extent of p53-dependent apoptosis.
Wild-type p53(+ / +) and heterozygous p53(+ / -) mice were exposed to X-rays at the mid-gestational period. The incidence of anomalies and prenatal deaths, the extent of apoptosis, and the levels of p53 protein were assessed.
After X-irradiation with 2 Gy, the incidence of malformation (corrected for control levels) was 0 and 30%, respectively, for p53(+ / +) and p53(+ / -). After irradiation of p53(+ / +) foetuses with 3 Gy, the frequency (F) of apoptotic cells rapidly peaked at 80% at 4 h and fell close to the control level at 48 h. The relationship between F 4h after irradiation and dose (D) (1-3Gy) is accurately expressed by a single-hit equation, F= 1 -exp ( -(a + bD)¿, where the radiation-induced apoptosis rate, b, is 0.47 for the wild type and 0.22 for the heterozygous mice. The X-irradiated foetuses showed no increase in the levels of p53 protein.
The higher susceptibility of irradiated p53(+ / -) foetuses to malformation is related to a twofold lower rate of apoptosis; competent removal by apoptosis of damaged cells from irradiated tissues is impaired dramatically if one of two wild-type p53 alleles is lost. The frequency of apoptotic cells in the wild type reached a maximum 4h after foetal irradiation with no measurable increase in the level of p53 protein, indicating that radiation-induced p53-mediated foetal apoptosis depends on non-transcriptional events.
研究辐射诱导畸形的发生率与p53依赖性细胞凋亡程度之间的关系。
在妊娠中期对野生型p53(+/+)和杂合型p53(+/-)小鼠进行X射线照射。评估异常和产前死亡的发生率、细胞凋亡程度以及p53蛋白水平。
经2 Gy X射线照射后，p53(+/+)和p53(+/-)的畸形发生率（校正对照水平后）分别为0和30%。用3 Gy照射p53(+/+)胎儿后，凋亡细胞频率（F）在4小时时迅速达到峰值80%，并在48小时时降至接近对照水平。照射后4小时的F与剂量（D）（1 - 3 Gy）之间的关系可由单打击方程准确表示，F = 1 - exp(-(a + bD))，其中野生型的辐射诱导细胞凋亡率b为0.47，杂合型小鼠为0.22。X射线照射的胎儿p53蛋白水平未升高。
受照射的p53(+/-)胎儿对畸形的更高易感性与细胞凋亡率降低两倍有关；如果两个野生型p53等位基因中的一个缺失，通过细胞凋亡从受照射组织中有效清除受损细胞的能力会显著受损。野生型胎儿照射后4小时凋亡细胞频率达到最大值，而p53蛋白水平无明显升高，表明辐射诱导的p53介导的胎儿细胞凋亡依赖于非转录事件。
