p53-dependent apoptosis suppresses radiation-induced teratogenesis

p53依赖性细胞凋亡抑制辐射诱导的致畸作用

• 批准号: 06454641
• 负责人: NORIMURA Toshiyuki
• 金额: $ 3.52万
• 依托单位: University of Occupational and Environmental Health
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06454641/
• 关键词: p53 gene; phenotypical anomalies; apoptosis; X-rays; prenatal death; teratogenesis; p53-deficient mice; 催奇性傷害; 催奇性障害

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 wildtype (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，大约一半的人类受孕没有被植入子宫，导致无法识别的自然流产，大约5%的人类出生有可识别的畸形。为了寻找畸形和流产机制的线索，我们比较了P53基因缺失(P53^&lt；-/-&gt；)和野生型(P53^&lt；+/+&gt；)小鼠辐射致畸形和流产的发生率。在妊娠9.5天接受2GyX射线照射后，P53^&lt；-/-&gt；小鼠的异常发生率为70%，死亡发生率为7%，而p53^-lt；+/+&gt；小鼠的异常发生率为20%，死亡发生率为60%。在妊娠3.5天照射后也有类似的结果。对异常和胚胎或胎儿致死性的辐射敏感性的这种相互关系支持这样一种观点，即胚胎或胎儿组织有一个依赖于p53的组织守护人，该组织负责流产承担辐射诱导的致畸DNA损伤的细胞。事实上，X射线照射后，P53^&lt；+/+&gt；胎儿组织中含有凋亡DNA片段的细胞数量显著增加，但在P53^&lt；-/-&gt；胎儿组织中未见明显变化。

项目成果

T. Norimura, S. Nomoto, M. Katsuki, Y. Gondo & S. Kondo: "p53-dependent apoptosis suppresses radiation-induced teratogenesis" Nature Medicine. 2. 577-580 (1996)

T. Norimura、S. Nomoto、M. Katsuki、Y. Gondo

法村俊之,野元 諭: "放射線催奇性障害に対するアポトーシスの役割" 医学のあゆみ. 177. 536-537 (1996)

Toshiyuki Homura、Satoshi Nomoto：“细胞凋亡在放射性致畸疾病中的作用”医学史 177. 536-537 (1996)。

Toshiyuki NORIMURA: "p53-dependent apoptosis suppresses radiation-induced teratogenesis." Nature Medicine. (acceptable for publication). (1996)

Toshiyuki NORIMURA：“p53 依赖性细胞凋亡抑制辐射诱导的畸胎发生。”

Sohei Kondo, Toshiyuki Norimura, Taisei Nomura: "Programd cell death for defense against anomaly and tumor formation." TRANSACTIONS of the American Nuclear Society. 73. 37-38 (1995)

Sohei Kondo、Toshiyuki Norimura、Taisei Nomura：“用于防御异常和肿瘤形成的程序性细胞死亡。”

Sohei KONDO: "Programmed cell death for defense against anomaly and tumor formation." TRANSACTIONS of the American Nuclear Society. 73. 37-38 (1995)

Sohei KONDO：“通过程序性细胞死亡来防御异常和肿瘤形成。”