Lindegaard J C, Nielsen O S
Danish Cancer Society, Department of Experimental Clinical Oncology, Radiumstationen, Aarhus C, Denmark.
Int J Radiat Oncol Biol Phys. 1991 May;20(5):1023-9. doi: 10.1016/0360-3016(91)90200-n.
The effect of step-down heating was investigated in the skin of the CDF1 mouse foot. Step-down heating was induced with a 44.7 degrees C/10 min pretreatment followed by a test treatment at a lower temperature for variable time. Step-up heating, that is, a test treatment followed by a 44.7 degrees C/10 min treatment, and single heating were used as controls. The normal tissue reaction was scored at five levels of damage (from slight redness and oedema to loss of a toe or greater reaction), and the heating time to induce each level in 50% of the animals, RD50, was used as the endpoint. The effect of step-down heating was quantified by the step-down ratio, calculated as the ratio of test heating times to obtain the endpoint. A significant reduction of the RD50 was seen at all score levels when the 44.7 degrees C/10 min was given in a step-down heating schedule, and the effect increased with decreasing test treatment temperature. In contrast, the heat sensitivity was only marginally influenced by step-up heating. An analysis of the time-temperature relationship demonstrated a log-linear relationship between temperature and RD50 for single heating in the range 42.2-44.7 degrees C and for step-down heating in the range 41.7-44.7 degrees C. The curve for step-down heating showed a lesser slope indicating a decrease of the activation energy. The kinetics of the SDH effect were investigated by inserting an interval between a primary 44.7 degrees C/10 min treatment and a test treatment performed at 42.2 degrees C. The effect of step-down heating was maximal with no interval between the priming treatment and the test treatment. As the interval was increased to 1.5 hr the step-down sensitization disappeared, and with even longer intervals thermotolerance developed. From a clinical point of view, the present data indicate that step-down heating may increase the extent of both reversible and irreversible heat damage in the normal tissue.
研究了逐步降温加热对CDF1小鼠足部皮肤的影响。通过44.7℃/10分钟的预处理诱导逐步降温加热，随后在较低温度下进行不同时间的测试处理。逐步升温加热（即先进行测试处理，然后进行44.7℃/10分钟的处理）和单次加热用作对照。正常组织反应按五级损伤评分（从轻微发红和水肿到脚趾缺失或更严重反应），将50%的动物诱导至各损伤级别的加热时间，即RD50，用作终点指标。逐步降温加热的效果通过逐步降温比来量化，计算方法为获得终点指标的测试加热时间之比。当在逐步降温加热方案中进行44.7℃/10分钟的处理时，在所有评分级别均观察到RD50显著降低，且随着测试处理温度的降低效果增强。相比之下，逐步升温加热对热敏感性的影响很小。时间-温度关系分析表明，在42.2-44.7℃范围内单次加热以及在41.7-44.7℃范围内逐步降温加热时，温度与RD50之间呈对数线性关系。逐步降温加热的曲线斜率较小，表明活化能降低。通过在初次44.7℃/10分钟处理和42.2℃的测试处理之间插入一个间隔来研究SDH效应的动力学。在引发处理和测试处理之间无间隔时，逐步降温加热的效果最大。随着间隔增加到1.5小时，逐步降温致敏消失，间隔更长时则产生热耐受性。从临床角度来看，目前的数据表明逐步降温加热可能会增加正常组织中可逆性和不可逆性热损伤的程度。
