Effects of Pre-exposure on the Survival and Hematological Changes in the Lethally Irradiated C57BL Mice

Exposing mice to 0.5 Gy 2 weeks before lethal (around LD50/30) whole-body irradiation has been reported to induce marked radio-resistance and to rescue them from "bone marrow death." It is widely accepted that cause of the death after dose around LD50/30 is mainly mediated by hematological failure. In order to elucidate the mechanism underlying the adaptive response, we examined effects of 0.5 Gy pre-exposure on the survival and hematological changes in C57BL mice irradiated with 6.5 Gy X-rays. The pre-exposure 2 weeks before the challenging dose enhanced survival to 77% at day 30, whereas without exposure, the survival decreased to 20 % at day 20 and 0% at day 26 after 6.5 Gy. Hematopoietic progenitor CFU-GM in the pre-irradiated mice began to recover around day 20 and then increased markedly. However, peripheral blood cell counts depleted to reach a nadir at day 20, regardless of the pre-irradiation, in spite of marked difference in the survival between the pre-irradiated and non-pre-irradiated mice. These cell counts in the pre-exposed mice recovered at day 30. We found that OK432, a bio-response modifier, could further enhance the survival of pre-exposed mice to 97%, when administrated 2 days before 0.5 Gy. The OK432 administrated mice also survived without recovery of the peripheral blood cell counts at day 20. These results manifest that the lethally irradiated mice are rescued by pre-exposure without recovery of hematological failure at least by day 20. Furthermore, we have observed long-term effect of pre-exposure for 1 year. More than half of the survivor of the pre-irradiated mice and the OK432 injected mice survived 1 year, even though they showed a variety of abnormalities.低線量放射線の生物影響に関する国際シンポジウ