p53-dependent apoptosis suppresses radiation-induced teratogenesis.
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.
Norimura
T
T
Department of Radiation Biology & Health, School of Medicine, University of Occupational & Environmental Health, Kitakyushu, Japan.
Nomoto
S
S
Katsuki
M
M
Gondo
Y
Y
Kondo
S
S
D000818:Animals; D017209:Apoptosis; D004622:Embryo, Mammalian / Q000002:abnormalities*; D005313:Fetal Death / Q000662:veterinary; D017880:Limb Deformities, Congenital; D051379:Mice; D008822:Mice, Transgenic; D009436:Neural Tube Defects; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency* / Q000235:genetics; D014965:X-Rays / Q000009:adverse effects
D016159:Tumor Suppressor Protein p53