Lindegaard J C, Nielsen O S, Overgaard J
Department of Experimental Clinical Oncology, Arhus Kommune Hospital, Denmark.
Int J Hyperthermia. 1995 Mar-Apr;11(2):231-9. doi: 10.3109/02656739509022459.
The effects of step-down (SDH) and step-up heating (SUH) on the development of thermotolerance were investigated in a C3H mammary carcinoma in vivo. The endpoint was tumour growth time, i.e. the time for a tumour to reach a volume five times that of the first treatment day. SDH consisted of 44.5 degrees C/5 min followed immediately by 41.0 degrees C/120 min. SUH consisted of the same heat treatments but in reverse sequence. Thermotolerance was detected by subsequent heating at 43.5 degrees C at variable intervals following the primary SDH or SUH. The degree of thermotolerance was quantified by the thermotolerance ratio (TTR) calculated as a ratio between the slope of the dose-response curve for tumours heated at 43.5 degrees C and tumours preheated with either SDH or SUH followed by 43.5 degrees C. Both SDH and SUH induced thermotolerance. However, the maximal degree of thermotolerance and the time interval to reach maximum thermotolerance were different. For SUH maximal thermotolerance was observed at 8 h with a TTR of 3.6. For SUH, thermotolerance peaked at 24-28 h with a TTR of 7.3. In both cases thermotolerance had decayed with a 120 h interval. The SDH priming induced about 2.5 times more heat damage than SUH. The results are therefore in agreement with previous data obtained in the same tumour model by single heating showing that both the degree and the time to reach maximal thermotolerance increases with pretreatment heat damage. In addition, the results indicate that thermotolerance and thermosensitization are independent phenomena.
在体内的C3H乳腺癌中研究了逐步降温（SDH）和逐步升温（SUH）对热耐受性发展的影响。终点是肿瘤生长时间，即肿瘤达到首次治疗日体积五倍所需的时间。SDH包括44.5℃/5分钟，随后立即是41.0℃/120分钟。SUH由相同的热处理组成，但顺序相反。在初次SDH或SUH之后，以可变间隔在43.5℃进行后续加热来检测热耐受性。热耐受性程度通过热耐受性比率（TTR）进行量化，该比率计算为在43.5℃加热的肿瘤与先用SDH或SUH预热后再在43.5℃加热的肿瘤的剂量反应曲线斜率之比。SDH和SUH均诱导了热耐受性。然而，最大热耐受性程度和达到最大热耐受性的时间间隔不同。对于SUH，在8小时时观察到最大热耐受性，TTR为3.6。对于SDH，热耐受性在24 - 28小时达到峰值，TTR为7.3。在两种情况下，热耐受性在120小时的间隔后均衰减。SDH预处理诱导的热损伤比SUH多约2.5倍。因此，这些结果与之前在同一肿瘤模型中通过单次加热获得的数据一致，表明达到最大热耐受性的程度和时间均随预处理热损伤而增加。此外，结果表明热耐受性和热敏化是独立的现象。
