Chapters authored
Dietary Modification of Mouse Response to Total-Body-Irradiation
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 30-day 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 7.5 Gy regardless the priming low dose at 0.5 Gy. When comparing the LD50 in the 30-day survival test, the LD50 values for the animals fed with the MB-1, HFD32 diet, and CE-2 Low Fat were 7.1 Gy, 6.0 Gy, and 6.2 Gy, respectively. As to the micronucleus test, for the mice fed with MB-1, the priming low dose at 0.5 Gy could significantly reduce the incidence of micronucleated erythrocytes in bone marrow that were caused by a challenge high dose at 4.0 Gy, while for the mice fed with either HFD32 or CE-2 Low Fat no such effect was observed. These findings indicated that under an unbalanced diet, namely, either of very high fat or of very low fat, alterations in mouse responses to TBI were induced. These findings confirmed that diet played a pivotal role in the response of the animals to radiation exposure, and suggested the possibility to modulate radiosensitivity through diet intervention in humans.
Part of the book: Evolution of Ionizing Radiation Research