van Rijn J, van den Berg J, Wiegant F A, van Wijk R
Department of Radiation Oncology, Free University Hospital, Amsterdam, The Netherlands.
Int J Hyperthermia. 1994 Sep-Oct;10(5):643-52. doi: 10.3109/02656739409022444.
Normal and thermotolerant H35 cells were submitted to step-down heating (SDH). SDH can significantly reduce the induction and expression of thermotolerance. For SDH a sensitizing treatment (ST) at 44.6 degrees C was followed by a test treatment (TT) at a lower hyperthermic temperature. The comparison between the thermotolerant and non-thermotolerant condition was based on isosurvival ST doses. For both conditions dose-effect relationships were obtained by plotting the ST-surviving fraction against the D0 of a TT. The TT was at either 41 or 42.5 degrees C, representing respectively, a permissive or a non-permissive condition for chronic induction of thermotolerance (CIT). The complex dose-effect relationships are partly exponential. In non-thermotolerant cells tested at 42.5 degrees C the dose-effect relationship between ST and TT is relatively weak. At 41 degrees C, however, the expression of CIT is strongly inhibited after a ST that kills < 20% of the cells. At higher ST doses the response is comparable with that at 42.5 degrees C. In thermotolerant cells a high degree of thermosensitization is also observed for relatively low ST doses, but in contrast with non-thermotolerant cells a stronger dose-effect relationship remains at the higher ST doses. Ultimately this results in a comparatively higher degree of thermosensitization that can be achieved in non-thermotolerant cells. For example, at an isosurviving fraction of 0.15 the reduction of D0 is non-thermotolerant cells at 42.5 degrees C is less than five times, whereas in thermotolerant cells, the D0 reduction is between 40 and 50 times. A similar reduction is found in non-thermotolerant cells tested at 41 degrees C. Subsequently, an isosurvival ST dose of about 40% was used in combination with a TT that was varied between 39 and 44 degrees C. D0's were plotted in an Arrhenius diagram to obtain a time-temperature relationship for the effect of SDH on thermotolerant and non-thermotolerant cells. The four plots are all biphasic with a downward inflection. Thermotolerance causes an upward shift of the inflection point of 2 degrees C relative to single-heated cells, whereas SDH causes a downward shift of 1 degree C in single-heated cells and of 2 degrees C in thermotolerant cells. For most of the temperature range, i.e. 39-43.5 degrees C, SDH decreases the activation energies.
将正常和耐热的H35细胞进行逐步降温加热（SDH）。SDH可显著降低热耐受性的诱导和表达。对于SDH，先在44.6℃进行敏化处理（ST），然后在较低的高温温度下进行测试处理（TT）。耐热和非耐热条件之间的比较基于等存活ST剂量。对于这两种条件，通过绘制ST存活分数与TT的D0值来获得剂量效应关系。TT温度为41℃或42.5℃，分别代表慢性诱导热耐受性（CIT）的允许或非允许条件。复杂的剂量效应关系部分呈指数关系。在42.5℃测试的非耐热细胞中，ST和TT之间的剂量效应关系相对较弱。然而，在41℃时，杀死<20%细胞的ST后，CIT的表达受到强烈抑制。在较高的ST剂量下，反应与42.5℃时相当。在耐热细胞中，对于相对较低的ST剂量也观察到高度的热敏化，但与非耐热细胞不同的是，在较高的ST剂量下仍保持较强的剂量效应关系。最终，这导致在非耐热细胞中可实现相对较高程度的热敏化。例如，在等存活分数为0.15时，42.5℃下非耐热细胞的D0降低不到5倍，而在耐热细胞中，D0降低在40至50倍之间。在41℃测试的非耐热细胞中也发现了类似的降低。随后，使用约40%的等存活ST剂量与在39至44℃之间变化的TT相结合。将D0值绘制在阿累尼乌斯图中，以获得SDH对耐热和非耐热细胞影响的时间-温度关系。这四个图都是双相的，有一个向下的拐点。热耐受性导致拐点相对于单次加热细胞向上移动2℃，而SDH导致单次加热细胞的拐点向下移动1℃，耐热细胞的拐点向下移动2℃。在大多数温度范围内，即39 - 43.5℃，SDH降低了活化能。
