Armour E, Wang Z, Corry P, Martinez A
Department of Radiation Oncology, William Beaumont Hospital, Royal, MI 48073.
Int J Hyperthermia. 1994 May-Jun;10(3):315-24. doi: 10.3109/02656739409010275.
Clinical application of long duration hyperthermia at temperatures < 42 degrees C has traditionally been avoided because of the possibility of chronic thermotolerance development, such as is observed with rodent cells. In support of long duration hyperthermia, both rodent and human cells have been shown to be sensitized to low dose-rate irradiation by simultaneous heating at 40 or 41 degrees C. The relationship between these supposed contradictory responses to hyperthermia were investigated in rat 9L gliosarcoma cells in vitro. Thermotolerance developed during 41 degrees C heating with or without concurrent low dose-rate irradiation. Thermotolerance reached a maximum within 6 h during 41 degrees C heating and remained stable for at least 24 h. When cells were returned to 37 degrees C after heating at 41 degrees C for 6 h, thermotolerance remained stable for at least 12 h. The time course of thermotolerance development correlated with that of induction of 41 degrees C radiation sensitization. Radiation sensitization, on the other hand, was shown to be independent of thermotolerance because the protein synthesis inhibitor cycloheximide prevented thermotolerance induction but had no effect on radiation sensitization. We conclude that thermotolerance development during concurrent clinical application of long duration mild temperature hyperthermia and low dose-rate irradiation should not be a factor in altering treatment outcome.
传统上，由于可能会出现慢性耐热性，如在啮齿动物细胞中观察到的那样，因此一直避免在低于42摄氏度的温度下长时间进行热疗的临床应用。支持长时间热疗的是，啮齿动物和人类细胞在40或41摄氏度同时加热时，已被证明对低剂量率辐射敏感。在体外大鼠9L胶质肉瘤细胞中研究了这些对热疗看似矛盾的反应之间的关系。在41摄氏度加热期间，无论是否同时进行低剂量率辐射，都会产生耐热性。在41摄氏度加热期间，耐热性在6小时内达到最大值，并至少保持稳定24小时。当细胞在41摄氏度加热6小时后恢复到37摄氏度时，耐热性至少保持稳定12小时。耐热性发展的时间进程与41摄氏度辐射增敏诱导的时间进程相关。另一方面，辐射增敏被证明与耐热性无关，因为蛋白质合成抑制剂环己酰亚胺可阻止耐热性诱导，但对辐射增敏没有影响。我们得出结论，在长时间温和温度热疗和低剂量率辐射的同时临床应用期间，耐热性的发展不应成为改变治疗结果的一个因素。
