Diet-induced Obesity Disturbs Epigenetic Responses to Ionizing Radiation in Mouse

Both exposure to ionizing radiation and obesity have been associated with various pathologies including cancer. There is a crucial need in better understanding the interactions between ionizing radiation effects (especially at low doses) and other risk factors, such as obesity. In order to evaluate radiation responses in obese animals, C3H and C57BL/6 mice fed a control low fat or a high fat (HF) diet were exposed to fractionated doses of X-rays (4×0.75 Gy). Bone marrow micronucleus assays did not suggest a modulation of radiation-induced genotoxicity by HF diet. Both HF diet and irradiation resulted in increased oxidative damage, H2AX levels and proliferation in C57BL/6 mouse liver. Using methylation-specific PCR, we observed that the promoters of p16 and Dapk genes were methylated in the livers of C57BL/6 mice fed a HF diet (irradiated and non-irradiated); Mgmt promoter was methylated in irradiated and/or HF diet-fed mice. In addition, methylation PCR arrays identified Ep300 and Socs1 (whose promoters exhibited higher methylation levels in non-irradiated HF diet-fed mice) as potential targets for further studies. We then compared microRNA regulations after radiation exposure in the livers of C57BL/6 mice fed a normal or an HF diet, using microRNA arrays. Interestingly, radiation-triggered microRNA regulations observed in normal mice were not observed in obese mice. All together, our results suggested the existence of dietary effects on radiation responses (especially epigenetic regulations) in mice, possibly in relationship with obesity-induced chronic oxidative stress. C57BL/6J mice were fed a normal or a high-fat diet and exposed to 4 x 0.75 Gy X-rays. miRNA expression was measured in the livers of 3 mice for each experimental group.