Abstract
Effects of low-dose radiation have been evaluated in changes of molecular levels, however, relationship of its change with biological phenomenon such as adaptive responses, radioresistance or carcinogenesis remains unclear. We have previously reported that, in the presence of insulin, MCF7 cells (human breast cancer cells) appear to be sensitive to low-dose irradiation (0.25 Gy) in MTS assays, which is based on measuring the total viable cell number. Using colony-forming assays, however, no change in the cell survival was observed. These results suggest that insulin induces growth inhibition in the cells after low-dose irradiation. As phosphatidylinositol 3 (PI3)-kinase is a know participant in insulin-related signaling cascades, effects of a PI3 kinase inhibitor on the insulin mediation were evaluated. LY294002, one of PI3-kinase inhibitors sensitized to irradiation with 0.25 Gy in the absence of insulin, similarly to the insulin mediation. These results suggest that PI3-kinase works to maintain cell growth after low-dose-irradiation, and the function is possibly inhibited in the presence of insulin. In addition, microarray analyses in the presence or the absence of insulin were performed and three genes were identified as altered genes whose expressions were increased by more than two folds after irradiation in the absence of insulin and had almost no change after irradiation in the presence of insulin. Roles of PI3 kinase or the gene expression will be discussed in low-dose radiation-induced signaling cascades.