KH-3, a novel chemical modulator of p53, enhances p21 induction and protects mice from gastrointestinal death by abdominal irradiation.

Modification of high-dose total body irradiation (TBI)-induced genotoxic effects by priming low-dose TBI and diet intervention was studied in a mouse model of radiation-induced adaptive response (AR). We aimed at finding the diet intervention condition under which the priming irradiation could most efficiently relieve the detrimental late genotoxic effect induced by the challenge high-dose of irradiations. Six-week old C57BL/6J female mice were X-irradiated with a priming dose at 0.5 Gy followed 2 weeks later by a challenge dose at 7.5 Gy. Three kinds of diet were used including a standard diet, a high fat diet and a very low fat diet. For the mice fed with the standard diet, diet restriction was performed at 15%, 25%, 50% and 75% compared to the non-restriction group (100%). The animals were treated under these diet conditions from weaning to the end of the experiment. A challenge dose at 4.0 Gy was used in the study on the genotoxic effect in surviving animals by measurement of the micronucleated erythrocytes in the bone marrow. AR was observed in the animals fed with the standard diet without restriction and at 15% and 25% restriction. Animals with 15% diet restriction showed similar 30-day survival curve compared to those without restriction, while animals with 25% diet restriction showed increased radiosensitivities. On the other hand, AR was not demonstrated in the animals fed with high fat diet or very low fat diet, neither the animals fed with the standard diet at restriction of 50% and 75%. Study on the genotoxic effects showed that a mild restriction of the standard diet at 15% induced most efficiently suppressed genotoxic effects in animals both from the AR group and those receiving only the challenge dose. Results showed that diet intervention played a pivotal role in the response of the animals to radiation exposure, namely, a mild diet restriction could further suppress the delayed genotoxic effects from high dose radiation in the mouse AR model, while unbalanced diets and malnutrition could increase the radiosensitivities and even abolished a successful AR induction. These findings indicated that diet intervention could be a potential modifiable factor to detrimental radiation effects, and lifestyle management would be the initial therapies recommended for reducing risk from exposure to high-dose irradiations.\nKeywords: Radiation, Adaptive Response, Mouse, Diet Management, Genotoxic effects日本放射線影響学会第58回大会(学会出席・発表)参加日程: 平成27年5月25日〜29