Novel Method for Establishing a Beagle Dog Model of GI-ARS

Abstract The widespread use of nuclear energy and nuclear facilities has dramatically increased the risks associated with nuclear radiation exposure. Effective radioprotective agents that are easy to administer and have low toxicity are urgently needed to minimize the significant harm caused by exposure to nuclear radiation. Appropriate animal models are also required for investigation of the effectiveness of radioprotective agents. However, the animal models presently used to study the intestinal form of acute radiation sickness (ARS) are limited mainly to rodents, and large animal models (for example, Beagle dogs and non-human primates) are still under exploration. We have developed a Beagle model for investigation of GI-ARS in which the head, chest, and extremities are shielded to reduce the possibility of bleeding and/or damage to other more sensitive organs and rehydration support is provided after irradiation of 12.5 Gy with 60Co γ-rays. Significant vomiting and diarrhea were seen in this model, with typical signs of radiation sickness that progressively worsened with time since irradiation. The 6-day mortality rate was 100%, and significant intestinal damage was observed on gross autopsy and histopathology. By reflecting GI-ARS based on relatively objective evaluation of clinical manifestations and histopathological examination, this model provides a new concept and methodology for further experimental evaluation of the effectiveness of radioprotective agents in animals.