Keiko Haginoya

Adaptive Response in Embryogenesis. III. Relationship to Radiation-Induced Apoptosis and Trp53 Gene Status

Abstract Wang, B., Ohyama, H., Haginoya, K., Odaka, T., Itsukaichi, H., Yukawa, O., Yamada, T. and Hayata, I. Adaptive Response in Embryogenesis. III. Relationship to Radiation-Induced Apoptosis and Trp53 Gene Status. We reported previously that a radiation-induced adaptive response existed in the late period of embryogenesis, and that radiation-induced apoptosis in the predigital regions was responsible for digital defects in embryonic ICR mice. To investigate the possible involvement of the Trp53 gene and radiation-induced apoptosis in radiation-induced adaptive responses in embryogenesis, the present study was conducted using Trp53 wild-type (Trp53+/+) and Trp53 heterozygous (Trp53+/–) embryonic mice of the C57BL/6 strain. The existence of a radioadaptive response in the Trp53+/+ embryonic mice was demonstrated by irradiating the embryos with 5 or 30 cGy on embryonic day 11 prior to a challenging irradiation at 3 Gy on embryonic day 12. The two conditioning doses at 5 and 30 cGy significantly suppressed the induction of apoptosis by the challenging dose in the predigital regions of limb buds in the Trp53+/+ embryonic mice, while no such effect was found in the Trp53+/– embryonic mice. These findings indicate that induction of a radioadaptive response in embryogenesis is related to Trp53 gene status and the occurrence of radiation-induced apoptosis.

Prenatal Radiation-Induced Limb Defects Mediated by Trp53-Dependent Apoptosis in Mice

Abstract Wang, B., Ohyama, H., Haginoya, K., Odaka, T., Yamada, T. and Hayata, I. Prenatal Radiation-Induced Limb Defects Mediated by Trp53-Dependent Apoptosis in Mice. We reported previously that in utero radiation-induced apoptosis in the predigital regions of embryonic limb buds was responsible for digital defects in mice. To investigate the possible involvement of the Trp53 gene, the present study was conducted using embryonic C57BL/6J mice with different Trp53 status. Susceptibility to radiation-induced apoptosis in the predigital regions and digital defects depended on both Trp53 status and the radiation dose; i.e., Trp53 wild-type (Trp53+/+) mice appeared to be the most sensitive, Trp53 heterozygous (Trp53+/–) mice were intermediate, and Trp53 knockout (Trp53–/–) mice were the most resistant. These results indicate that induction of apoptosis and digital defects by prenatal irradiation in the later period of organogenesis are mediated by the Trp53 gene. These findings suggest that the wild-type Trp53 gene may be an intrinsic genetic susceptibility factor that is responsible for certain congenital defects induced by prenatal irradiation.

Adaptive response in embryogenesis: II. Retardation of postnatal development of prenatally irradiated mice.

We previously reported that a priming dose of 0.3 Gy on gestation day 11 significantly increased the rate of living fetuses and reduced the incidence of congenital malformations caused by exposure to 5 Gy X rays on gestation day 12 in ICR mice. In the present study, postnatal development of the live offspring was investigated using a set of developmental and behavioral parameters. The offspring of the mice irradiated with 0.3 Gy generally showed a delay in the appearance of most of the physiological markers, impaired acquisition of neonatal reflexes, and alteration of adult behavior. However, an increase in body weight in the females was observed 4 weeks postnatally. In the offspring primed with 0.3 Gy followed by a challenging dose of 5 Gy prenatally, a high postnatal mortality was found, and all the survivors had various radiation-induced detrimental effects. The results indicated that the priming dose was advantageous to survival itself, but was disadvantageous to the health of survivor. The results also suggested that studying the whole animal can show the extent of the effects of radiation, i.e. quality of life, in a way that cellular or molecular studies cannot.