Meyer J L, Van Kersen I, Becker B, Hahn G M
Int J Radiat Oncol Biol Phys. 1985 May;11(5):973-81. doi: 10.1016/0360-3016(85)90120-8.
We have investigated the development of thermotolerance in both tumors and normal tissues after 41 degrees C for durations as brief as 15 minutes. The murine RIF tumor, treated by both local radiofrequency and systemic methods, was assayed for thermotolerance by both tumor growth and cell survival analyses. The murine leg and ear, treated by conductive methods, were assayed using pre-defined tissue damage scoring systems. All of these treatments quickly induced substantial levels of thermotolerance. In the tumor studies using local heating, RIF mean diameter doubling time decreased from 17.8 days to a minimum of 13.0 days with a 9 hr interval between 41.0 degrees C for 15 minutes and 44.0 degrees C for 30 minutes (9 hr D1-D2); cell survival increased from 1.2 X 10(-2) to 3.4 X 10(-1) (same interval). Both assays showed some degree of tolerance present immediately after 41.0 degrees C for 15, 30 or 60 minutes (0 hr D1-D2). In the tumor studies using systemic heating, the kinetic pattern of the induced tolerance was similar to that observed after local heating. In the leg studies, 41.0 degrees for 30 minutes increased the time at 45 degrees C necessary to induce a specified level of tissue damage (mean score of 7) by a maximum of 1.8 times (24 hr D1-D2). The kinetic pattern was similar to that for the tumors. In the ear studies, 41.0 degrees C for 30 minutes increased the time at 45 degrees C necessary to induce ear necrosis in 50% of animals by a maximum of 3.5 times (48 hr D1-D2). The peak tolerance level occurred later for the ears, which have a lower normal temperature of 28-30 degrees C, than for the tumors or legs. These results indicate that: thermotolerance can begin to appear in tumors during treatment if hyperthermia sessions involve initial low thermal exposures (near 41 degrees C) for 15 minutes or longer; thermotolerance can develop in tumors after systemic heating and occurs with a kinetic pattern similar to that following local heating; and normal tissues also can develop high levels of thermotolerance after similar thermal exposures.
我们研究了在41摄氏度下持续仅15分钟的热疗后肿瘤组织和正常组织耐热性的发展情况。通过局部射频和全身方法处理的小鼠RIF肿瘤，采用肿瘤生长分析和细胞存活分析两种方法来检测其耐热性。通过传导方法处理的小鼠腿部和耳部组织，使用预定义的组织损伤评分系统进行检测。所有这些处理均迅速诱导出显著水平的耐热性。在局部加热的肿瘤研究中，RIF肿瘤平均直径倍增时间从17.8天缩短至最短13.0天，在41.0摄氏度下加热15分钟与在44.0摄氏度下加热30分钟之间间隔9小时（9小时D1-D2）；细胞存活率从1.2×10⁻²增至3.4×10⁻¹（相同间隔）。两种检测方法均显示，在41.0摄氏度下加热15、30或60分钟（0小时D1-D2）后立即出现了一定程度的耐受性。在全身加热的肿瘤研究中，诱导耐受性的动力学模式与局部加热后观察到的相似。在腿部研究中，41.0摄氏度加热30分钟使诱导特定程度组织损伤（平均评分为7）所需的45摄氏度暴露时间最多增加了1.8倍（24小时D1-D2）。动力学模式与肿瘤研究相似。在耳部研究中，41.0摄氏度加热30分钟使50%的动物发生耳部坏死所需的45摄氏度暴露时间最多增加了3.5倍（48小时D1-D2）。耳部正常体温较低，为28 - 30摄氏度，其耐受性峰值出现的时间比肿瘤或腿部更晚。这些结果表明：如果热疗疗程包括最初在接近41摄氏度的低温下暴露15分钟或更长时间，那么在治疗过程中肿瘤可能开始出现耐热性；全身加热后肿瘤也能产生耐热性，且其动力学模式与局部加热后相似；在类似的热暴露后，正常组织同样能产生高水平的耐热性。
