title: Involvement of p53-dependent apoptosis in radiation teratogenesis and in the radioadaptive response in the late organogenesis of mice.
abstract: The irradiation of fetuses at the late period of organogenesis has been known to induce a dramatic increase in malformations. The mechanisms involved, however, have remained unclear for a long time. Using the mouse limb bud system, we first found that radiation-induced apoptosis is involved in the malformation, namely, radiation-induced apoptosis in the predigital regions of embryonic limb buds is responsible for digital defects in mice. An examination of embryonic C57BL/6J mice with different p53 (trp53) status enabled us to further find that susceptibility to radiation-induced apoptosis in the predigital regions and digital defects depend on both the p53 status and the radiation dose; p53 wild-type mice appeared to be the most sensitive, while p53 knockout mice were the most resistant. These results indicate that p53-dependent apoptosis mediates radiation-induced digital defects in the later organogenesis period. The existence of a radioadaptive response in embryonic mice, which has not been reported so far, was found by irradiating embryos with either 5 cGy or 30 cGy on embryonic day 11 prior to a challenging irradiation at 3 Gy on embryonic day 12. p53-heterozygous embryos did not show the radioadaptive response, indicating the involvement of p53 in the radioadaptive response in embryogenesis.
authors.affiliation: Division of Radiobiology and Biodosimetry, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage-ku, Chiba 263-8555, Japan. jp2813km@nirs.go.jp
authors.forename: B
authors.initials: B
authors.lastname: Wang
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D004622:Embryo, Mammalian / Q000502:physiology; D005314:Embryonic and Fetal Development; D051379:Mice / Q000196:embryology*; D009381:Neoplasms, Radiation-Induced / Q000503:physiopathology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
chemical_list: D016159:Tumor Suppressor Protein p53