1995 Fiscal Year Final Research Report Summary
p53-dependent apoptosis suppresses radiation-induced teratogenesis
| Project/Area Number |
06454641
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
環境影響評価(含放射線生物学)
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| Research Institution | University of Occupational and Environmental Health |
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Principal Investigator |
NORIMURA Toshiyuki Univ.Occup.& Environm. Health, Sch.Med., Professor, 医学部, 教授 (20039530)
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| Co-Investigator(Kenkyū-buntansha) |
IMADA Hajime Univ.Occup.& Environm. Health, Sch.Med., Faculty Assistant, 医学部, 助手 (50223326)
GONDO Yoichi Tokai Univ., Inst.Med.Sci., Associate Professor, 総合医学研究所, 助教授 (40225678)
NOMOTO Satoshi Univ.Occup.& Environm. Health, Sch.Med., Faculty Assistant, 医学部, 助手 (90258608)
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| Project Period (FY) |
1994 – 1995
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| Keywords | p53 gene / phenotypical anomalies / apoptosis / X-rays / prenatal death / teratogenesis / p53-deficient mice / 催奇性傷害 |
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| Research Abstract |
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.
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