Raaphorst G P, Ng C E, Yang D P
Ottawa Regional Cancer Centre, Ontario, Canada.
Int J Hyperthermia. 1999 Jan-Feb;15(1):17-27. doi: 10.1080/026567399285828.
Human melanoma cells (SK-mel-3) were treated with combinations of radiation and hyperthermia treatment and survival (using the colony forming assay) and DNA double strand breaks (dsb's) (using pulsed field gel electrophoresis) were measured for immediate and delayed plating. The cells were treated in plateau phase, so that delayed plating would result in repair of potentially lethal damage (PLD). Delayed plating showed PLDR for both the survival and the dsb end-point. One hour of heating after irradiation showed a temperature dependent increase in radiosensitization for both the survival endpoint and the dsb endpoint for the temperature range from 42 to 45 degrees C. One hour of heating at 43 degrees C after irradiation resulted in the partial inhibition of PLDR and recovery of dsb's. For heating at 45 degrees C the inhibition of dsb repair was complete. There was good correlation between the survival endpoint and the dsb endpoint for the thermal radiosensitization for both the immediate plating and the PLDR protocols. These data indicate that hyperthermia inhibition of repair of PLD is probably due to the inhibition of dsb rejoining. These correlations were made at the same dose levels for survival and dsb analysis, thus avoiding the potential complications of many earlier studies which used much higher doses for dsb analysis than for survival studies.
将人黑色素瘤细胞（SK-mel-3）用放疗和热疗联合处理，并通过集落形成试验测量即时接种和延迟接种后的存活率，以及用脉冲场凝胶电泳测量DNA双链断裂（dsb）情况。细胞在平台期进行处理，这样延迟接种会导致潜在致死性损伤（PLD）的修复。延迟接种显示存活率和dsb终点均有潜在致死性损伤修复（PLDR）。照射后1小时加热显示，在42至45摄氏度的温度范围内，存活率终点和dsb终点的放射增敏作用均随温度升高而增加。照射后在43摄氏度加热1小时导致PLDR部分受抑制和dsb修复恢复。对于45摄氏度加热，dsb修复的抑制是完全的。即时接种和PLDR方案的热放射增敏作用在存活率终点和dsb终点之间有良好的相关性。这些数据表明，热疗对PLD修复的抑制可能是由于对dsb重新连接的抑制。这些相关性是在存活率和dsb分析的相同剂量水平下得出的，从而避免了许多早期研究中潜在的复杂情况，这些研究在dsb分析中使用的剂量比存活率研究高得多。
