Involvement of p53-Dependent Apoptosis in Radiation Teratogenesis and in the Radioadaptive Response in the Late Organogenesis of Mice

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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.
日本放射線影響学会の論文