Norimura T, Nomoto S, Katsuki M, Gondo Y, Kondo S
Department of Radiation Biology & Health, School of Medicine, University of Occupational & Environmental Health, Kitakyushu, Japan.
Nat Med. 1996 May;2(5):577-80. doi: 10.1038/nm0596-577.
About half of human conceptions are estimated not to be implanted in the uterus, resulting in unrecognizable spontaneous abortions, and about 5% of human births have a recognizable malformation. In order to find clues to the mechanisms of malformation and abortion, we compared the incidences of radiation-induced malformations and abortions in p53 null (p53-/-) and wild-type (p53+/+) mice. After X-irradiation with 2 Gy on day 9.5 of gestation, p53-/- mice showed a 70% incidence of anomalies and a 7% incidence of deaths, whereas p53+/+ mice had a 20% incidence of anomalies and a 60% incidence of deaths. Similar results were obtained after irradiation on day 3.5 of gestation. This reciprocal relationship of radiosensitivity to anomalies and to embryonic or fetal lethality supports the notion that embryonic or fetal tissues have a p53-dependent "guardian" of the tissue that aborts cells bearing radiation-induced teratogenic DNA damage. In fact, after X-irradiation, the number of cells with apoptotic DNA fragments was greatly increased in tissues of the p53+/+ fetuses but not in those of the p53-/- fetuses.
据估计，约一半的人类受精卵无法着床于子宫，导致难以察觉的自然流产，约5%的人类出生时有可识别的畸形。为了找到畸形和流产机制的线索，我们比较了p53基因敲除（p53-/-）小鼠和野生型（p53+/+）小鼠辐射诱导的畸形和流产发生率。在妊娠第9.5天接受2 Gy的X射线照射后，p53-/-小鼠的畸形发生率为70%，死亡率为7%，而p53+/+小鼠的畸形发生率为20%，死亡率为60%。在妊娠第3.5天照射后也得到了类似的结果。这种对畸形和胚胎或胎儿致死率的放射敏感性的相互关系支持了这样一种观点，即胚胎或胎儿组织具有一种依赖p53的“守护者”组织，该组织会使携带辐射诱导致畸DNA损伤的细胞流产。事实上，X射线照射后，p53+/+胎儿组织中具有凋亡DNA片段的细胞数量大幅增加，而p53-/-胎儿组织中则没有。
