LOW DOSE-RATE RADIATION-SPECIFIC ALTERATIONS FOUND IN A GENOME-WIDE GENE EXPRESSION ANALYSIS OF THE MOUSE LIVER.

Life span shortening and increased incidences of cancer and non-cancer diseases were observed in B6C3F1 mice irradiated with gamma-rays at a low dose-rate (LDR) of 20 mGy/d for 400 d. A genome-wide gene expression profiling of livers from mice irradiated at a LDR (20 mGy/d, 100-400 d) was performed. LDR radiation affected specific pathways such as those related to lipid metabolism, e.g. 'Cholesterol biosynthesis' and 'Adipogenesis' in females irradiated for 200 and 300 d at 20 mGy/d, with increased expression of genes encoding cholesterol biosynthesis enzymes (Cyp51, Sqle, Fdps) as age and radiation dose increased. No significant alterations in the expression of these genes were observed in male mice exposed similarly. However, the genes encoding adipogenesis regulators, Srebf1 and Pparg, increased with age and radiation dose in both sexes. Comparison between LDR-irradiated and medium dose-rate (400 mGy/d) male mice revealed quite different gene expression profiles. These results seem to be consistent with the increased incidence of fatty liver and obesity in female mice exposed to LDR radiation and suggest that metabolism is an important target of LDR radiation.