Dewey W C
Radiation Oncology Research Laboratory, University of California, San Francisco 94103.
Int J Hyperthermia. 1994 Jul-Aug;10(4):457-83. doi: 10.3109/02656739409009351.
There are great differences in heat sensitivity between different cell types and tissues. However, for an isoeffefct induced in a specific cell type or tissue by heating for different durations at different temperatures varying from 43-44 degrees C up to about 57 degrees C, the duration of heating must be increased by a factor of about 2 (R value) when the temperature is decreased by 1 degrees C. This same time-temperature relationship has been observed for heat inactivation of proteins, and changing only one amino acid out of 253 can shift the temperature for a given amount of protein denaturation from 46 degrees C to either 43 or 49 degrees C. For cytotoxic temperatures < 43-44 degrees C, R for mammalian cells and tissues is about 4-6. Many factors change the absolute heat sensitivity of mammalian cells by about 1 degrees C, but these factors have little effect on Rs, although the transition in R at 43-44 degrees C may be eliminated or shifted by about 1 degrees C. R for heat radiosensitization are similar to those above for heat cytotoxicity, but Rs for heat chemosensitization are much smaller (usually about 1.1-1.2). In practically all of the clinical trials that have been conducted, heat and radiation have been separated by 30-60 min, for which the primary effect should be heat cytotoxicity and not heat radiosensitization. Data are presented showing the clinical application of the thermal isoeffect dose (TID) concept in which different heating protocols for different times at different temperatures are converted into equiv min at 43 degrees C (EM43). For several heat treatments in the clinic, the TIDs for each treatment can be added to give a cumulative equiv min at 43 degrees C, viz., CEM43. This TID concept was applied by Oleson et al. in a retrospective analysis of clinical data, with the intent of using this approach prospectively to guide future clinical studies. Considerations of laboratory data and the large variations in temperature distributions observed in human tumours indicate that thermal tolerance, which has been observed for mammalian cells for both heat killing and heat radiosensitization, probably is not very important in the clinic.(ABSTRACT TRUNCATED AT 400 WORDS)
不同细胞类型和组织之间的热敏感性存在很大差异。然而，对于在43 - 44摄氏度至约57摄氏度的不同温度下加热不同持续时间，在特定细胞类型或组织中诱导产生的等效应而言，当温度降低1摄氏度时，加热持续时间必须增加约2倍（R值）。蛋白质的热失活也观察到了相同的时间 - 温度关系，并且在253个氨基酸中仅改变一个氨基酸，就可以使给定蛋白质变性量的温度从46摄氏度变为43或49摄氏度。对于细胞毒性温度<43 - 44摄氏度，哺乳动物细胞和组织的R约为4 - 6。许多因素会使哺乳动物细胞的绝对热敏感性改变约1摄氏度，但这些因素对R值影响很小，尽管在43 - 44摄氏度时R值的转变可能会被消除或偏移约1摄氏度。热放射增敏的R值与上述热细胞毒性的R值相似，但热化学增敏的R值要小得多（通常约为1.1 - 1.2）。在几乎所有已进行的临床试验中，热疗和放疗之间间隔30 - 60分钟，其主要效应应为热细胞毒性而非热放射增敏。文中给出的数据展示了热等效应剂量（TID）概念的临床应用，即将不同温度下不同时间的不同加热方案转换为43摄氏度下的等效分钟数（EM43）。对于临床上的几种热疗，每种治疗的TID可以相加得到43摄氏度下的累积等效分钟数，即CEM43。Oleson等人在对临床数据的回顾性分析中应用了这个TID概念，目的是前瞻性地使用这种方法来指导未来的临床研究。对实验室数据的考量以及在人类肿瘤中观察到的温度分布的巨大差异表明，哺乳动物细胞在热杀伤和热放射增敏方面都观察到的热耐受性，在临床上可能并不十分重要。（摘要截选至400字）
