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Nature Medicine  2, 577 - 580 (1996)

p53-dependent apoptosis suppresses radiation−induced teratogenesis

Toshiyuki Norimura1, 4, Satoshi Nomoto1, Motoya Katsuki2, Yoichi Gondo2 & Sohei Kondo3

  1Department of Radiation Biology or Health, School of Medicine, University of Occupational & Environmental Health, Japan, Yahatanishi-ku, Kitakyushu 807, Japan

  2Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka 812, Japan

  3Atomic Energy Research Institute, Kinki University, Higashiosaka, Osaka 577, Japan

  4Correspondence should be addressed to T.N.

About half of human conceptions are estimated not to be implanted in the uterus, resulting in unrecognizable spontaneous abortions1,2, and about 5% of human births have a recognizable malformation1,3. 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 tissue4 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.

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ISSN: 1078-8956
EISSN: 1546-170X
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