Radiobiological factors determining the radiosensitivity of radioresistant cancer cells

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In an attempt to elucidate the mechanism of radioresistance in melanoma cells, we demonstrated the following facts in the experimental system using human and murine melanoma cells : (1) the radiation dose-survival curve in melanoma cells had a larger shoulder portion in the low dose region, showing a marked radioresistance to doses commonly used in the conventional fractionated radiotherapy ; (2) melanoma cells showed a prominent repair of potentially lethal damage (PLD) after irradiation ; (3) melanoma cells had a relatively high fraction of S-phase cells which were more radioresistant than other phase cells in the cell cycle ; and, (4) pretreatment of melanoma cells with L-dopa significantly reduced the capacity for sublethal radiation damage in melanoma cells.On the basis of these results, we have studied the cell kinetics, melanin production, GSH metabolism, and DNA repair, so as to further elucidate the mechanism of radioresistance of melanoma cells. All of melanin-producing melanoma cell lines showede a larger shoulder portion in the low dose region and a larger repair of PLD in various conditioned examined. The synchronized culture method demonstrated the change of radiosensitivity during the cell cycle and the survival curves of cells in each phase of the cell cycle. GSH levels and GSH-related enzymes activity were examined, suggesting the relationship between the GSH metabolism and radiosensitivity. Further, unscheduled DNA synthesis (UDS) after irradiation were also examined, so as to elucidate the relationship between the DNA repair and radiosensitivity.