Radioactive Response and radiation-Induced Teratogenesis in the Late Period of Organogenesis in Mice: Involvement of p53-Dependent Apoptosis

In the past 5 years, a series of study was done at our institute toinvestigate radiation effects on the embryogenesis in mice with an emphasison mechanisms involved in the radiation-induced adaptive response and therole of radiation-induced apoptosis played in teratogenesis in the lateperiod of organogenesis. Using the limb bud system, we first found thatradiation-induced apoptosis is involved in malformations, namely,radiation-induced apoptosis in the predigital regions of embryonic limb budsis responsible for digital defects in ICR mice. Examination of embryonicC57BL/6J mice with different p53 status led to further finding thatsusceptibility to the radiation-induced apoptosis and digital defectsdepends on both the p53 status and the radiation dose. p53 wild-type miceappeared to be the most sensitive, while p53 knockout mice were the mostresistant. These results indicate that p53-dependent apoptosis mediatesradiation-induced digital defects. The existence of a radioadaptive responsein fetuses, i.e., the priming dose significantly decreases the apoptosisinduction, prenatal death, and digital defects in the living fetuses inducedby the challenging dose, was found first in ICR strain mice and laterconfirmed again in C57BL/6J mice. p53 heterozygous embryos did not show theradioadaptive response, indicating the involvement of p53 in theradioadaptive response