Dietary Modification of Mouse Response to Total-Body-Irradiation

Abstract

Exposure to ionizing radiation (IR) could induce deleterious effects including cancer. Diet, as one of the major factors to influence susceptibility to many diseases, plays a critical role in maintaining human heath. It is known that unbalanced diet could result in health consequences, for example, high-calorie diet could lead to obesity, which could increase the risk of diabetes, heart disease, fatty liver, and some forms of cancer. Although the impact of diet on susceptibility to IR is thought to be big, the evidence is not clear due to lack of study. In this work, effects from dietary fat on modulation of mouse responses to total-body-irradiation (TBI) were studied. The mice were fed after weaning at postnatal age of 4 weeks with a standard diet (MB-1), a very high-fat diet (HFD32), and a very low-fat diet (CE-2 Low Fat), containing of 4.4%, 32.0%, and 0.4% of crude fat, respectively. A mouse model for radiation-induced adaptive response (AR) was applied to this work. The priming low-dose TBI at a dose of 0.5 Gy from X-rays was given at postnatal age of 6 weeks, and the challenge high dose of TBI was given at postnatal age of 8 weeks. The mouse response to low dose of TBI was evaluated by the efficacy of the priming low dose to rescue the animals from bone marrow death induced by the challenge high dose in the 30-day survival test. The mouse response to high dose of TBI was evaluated by comparing the LD50 in the 30day survival test. In addition, dietary modulation of the residual (late) genotoxic effect from TBI was also evaluated by comparing the incidence of micronucleated erythrocytes in bone marrow using micronucleus test. Results showed that for the mice fed with the MB-1, a successful AR was demonstrated. While for the mice fed with either HFD32 or CE-2 Low Fat, no AR was observed, and all the animals died within 15 days after TBI with the challenge high dose at 7.

Reduced High-Dose Radiation-Induced Residual Genotoxic Damage by Induction of Radioadaptive Response and Prophylactic Mild Dietary Restriction in Mice

“…Our studies confirmed that there existed an interaction between life-style factors (i.e., high fat diet, low fat diet and alcohol drinking) and IR, which could lead to altered responses to IR in mice. 35 - 37 In the present work, combination of MDR and RAR was further verified in the mouse RAR model. Results indicated that MDR would not influence the phenotype of RAR measured as 30-day survival, and combined treatment with MDR and RAR could achieve a higher efficacy to relieve radiogenotoxicity and radiation-induced GI measured as reduced micronucleus frequency in the erythrocytes in the bone marrow.…”

“…Conversely, severe dietary restriction or malnutrition due to unbalanced diet could increase sensitivity of normal tissues to radiogenotoxicity, radiation-induced bone marrow death and life shortening in mice. 36 , 42 …”