Study of Fractionated Exposure Using Hyper-radiosensitivity for Application to Radiation Therapy

抄録

Enhanced cell lethality, also known as hyper-radiosensitivity (HRS), has been reported at low doses of radiation (0–0.5 Gy) in various cell lines and is expected to be an effective cancer therapy using HRS. It is necessary to study hyperfractionation in order to improve radiation therapy. However, the method of exposure using HRS is not established because the dose involved in HRS is too low for clinical application. We conducted this study to examine the effect of low-dose fractionation exposures with a short-time interval for clinical application. We evaluated the cell-survival rate of Chinese hamster V79 cells and human lung A549 cells using colony assays. We performed fractionation exposures in unit doses of 0.25, 0.5, 1.0, and 2.0 Gy. First, we exposed the cells to 2 Gy of X-rays at dose rates of 1.0, 1.5, and 2.0 Gy/min at 1-min intervals by fractionated radiation. Next, we exposed these cells to the radiation dose rate of 2.0 Gy/min at 10-s, 1-min, and 3-min intervals by fractionated radiation. Finally, the total doses of 2, 4, and 8 Gy were given by fractionated radiation at a dose rate of 2.0 Gy/min for 10 s. Apoptosis and cell cycle were also evaluated in fractionation exposures and compared with single exposure. Both cell survival rates with fractionation exposure using a unit dose of 0.25 Gy were remarkably low compared with those of a single exposure delivering the same dose. When the dose rates were lower (1.0 and 1.5 Gy/min), the cytotoxic effect decreased compared with exposure to a dose rate of 2.0 Gy/min. Significant cytotoxic effects were observed when A549 cells were exposed to low-dose fractionation (0.25 Gy×8) using 10-s, 1-min, and 3-min intervals compared with single exposure. On the other hand, the cytotoxic effect decreased when V79 cells were exposed to low-dose fractionation (0.25 Gy × 8) at 3-min intervals, compared with shorter time intervals (10 s and 1 min). When cells were exposed to total doses of 2, 4, and 8 Gy by fractionated radiation at the unit dose of 0.25, cytotoxicity was enhanced as the total dose increased up to 8 Gy. These results indicate that a more effective cell death is induced with low-dose fractionation exposures for a given dose due to the HRS phenomenon, thus suggesting that a dose rate was important for effective low-dose fractionation exposures.