Abstract
Radiation risk due to low dose-rate radiation has not been well established. It is generally considered that the animal study is a promising approach to this issue if it is combined with the study on mechanisms of radiation effects to extrapolate the animal data to human. Continuous low dose-rate irradiation of 4000 SPF mice for 400-days was carried out at IES, Japan, and it was reported that the life spans of mice irradiated at the dose-rate of 16 μGy/min were significantly shortened, but not at the dose-rate of 40 nGy/min. A significant life span-shortening in female mice irradiated at 800 nGy/min was observed. The observed life spans-shortening was due to early death from a variety of neoplasms and not from increased incidence of specific neoplasms. In order to investigate the molecular background for the life spans-shortening caused by low dose-rate irradiation, we examined the gene expression profile by using a cDNA microarray. By examining the de-regulated genes, it was found that activity of the mitochondrial respiration was elevated after irradiation at 650 nGy/min and 13 μGy/min in kidney. The resulting oxidative stress was thought to be one of the factors that cause early incidence of neoplasms. However it should be noted that alteration in the gene expression profile is different depending on the tissue. In testis, it was observed that genes related to the gene ontology categories of mitotic cell cycle, DNA replication, DNA repair, and response to DNA damage stimulus were down-regulated after 650 nGy/min and 13 μGy/min, and that genes related to heat-shock responses were up-regulated. It seemed as if the cells in testis were preparing for emergency by shutting down the general metabolisms as well as DNA repair functions. The molecular background for early incidence of neoplasms after low dose-rate irradiation may be different depending on target organs.
