55. Low Dose Pre-irradiation Reducing Prenatal Death and Congenital Malformation During the Late Period of Organogenesisi

Bing Wang, Harumi Ohyama, Keiko Haginoya, Takeko Odaka, Kaoru Tanaka, Eiichi Kojima, Takeshi Yamada^* and Isamu Hayata
(^*Toho Univ.)

Keywords: radioadaptation, organogenesis, prenatal death, malformations, mice

The adaptive response to ionizing radiation (radioadaptation) has been found in procaryotic and eucaryotic cells as well as in non-mammalian and mammalian systems, however, wether radioadaptation occurs during embryogenesis of mammalians is still uncertain.

In the present study, radioadaptation was demonstrated in embryogenesis of mice. Whole-body irradiation at the dose of 0-50 cGy was given for conditioning pregnant ICR mice on Day 9 to Day 11 of their gestation. Then their whole bodies were exposed to a challenging dose of 5 Gy on the next day. The numbers of living fetuses, prenatal deaths, and of living fetuses with external gross malformations were investigated on Day19. A conditioning dose of 30 cGy on Day 11 significantly increased the rate of living fetuses and reduced the incidence of congenital malformations. This indicates the existence of a critical dose and timing for conditioning in radioadaptation during the late period of organogenesis in mice.

The conditioning irradiation may have increased radioresistance of the fetuses by killing the radiosensitive cells which then reconstructed fetuses with a cquired radioresistant cells. Another assumption is that in decreased the speed of fetal development to allow the effective operation of cell-replacement repair when the challenging dose was given. A conditioning low dose pre-irradiation is believed to trigger changes in the expression of several genes whose products, though most of them are not yet identified, would be related to DNA repair and/or control of cell cycle progression, and induction of apoptosis. Further investigations on the mechanisms are underway.