Armour E P, Wang Z H, Corry P M, Martinez A
Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan 48073.
Cancer Res. 1991 Jun 15;51(12):3088-95.
Modification of survival by long duration, 41 degrees C hyperthermia in combination with low dose rate radiation (0.5 Gy/h) was determined in rat 9L gliosarcoma cells. Cells were exposed to radiation in a manner that simulated continuous irradiation at a dose rate relevant to clinical brachytherapy. High dose rate X-irradiation was fractionated in 1.0-Gy fractions at 2-h intervals (FLDRI). Previous studies had demonstrated that 9L cells exposed to FLDRI with these parameters have survival characteristics that are equivalent to continuous low dose rate irradiation. Cells exposed to 41 degrees C throughout FLDRI were sensitized significantly (thermal enhancement ratio of 2.07) compared with cells irradiated at 37 degrees C. Incubation for 24 h at 41 degrees C before and/or after FLDRI at either 37 degrees C or 41 degrees C did not increase the slope of the radiation survival curves but did reduce the shoulder. Similarly, heating at 43 degrees C for 30 or 60 min before and/or after irradiation at 0.5 Gy/h also did not enhance cell sensitivity. Survival of cells after irradiation at high dose rate (60 Gy/h) was independent of the temperature during irradiation. Preheat at 41 degrees C for 24 h did not sensitize cells to high dose rate irradiation by increasing the slope of the survival curve, although a loss of shoulder was observed. Sensitization of cells heated at 43 degrees C for 30 or 60 min before high dose rate irradiation was expressed as classical slope modification. Our results demonstrate that 41 degrees C heating during FLDRI greatly sensitizes cells to radiation-induced killing for exposure durations up to 36 h. Heating 9L cells at 41 degrees C or 43 degrees C adjacent to FLDRI at 0.5 Gy/h resulted in no additional enhancement of terminal sensitivity, although shoulder modification was observed. The sensitization by simultaneous heating described above occurred even though thermotolerance developed during extended incubation at 41 degrees C. These in vitro data demonstrate that simultaneous protracted heating at modest temperatures could greatly enhance the cytotoxic effects of low dose rate interstitial irradiation and could be of significance in clinical application.
在大鼠9L胶质肉瘤细胞中测定了长时间41℃高温与低剂量率辐射（0.5Gy/h）联合对细胞存活的影响。细胞接受辐射的方式模拟了临床近距离治疗中相关剂量率的连续照射。高剂量率X射线照射以1.0Gy分次，间隔2小时进行（FLDRI）。先前的研究表明，暴露于这些参数的FLDRI的9L细胞具有与连续低剂量率照射相当的存活特征。与在37℃照射的细胞相比，在整个FLDRI过程中暴露于41℃的细胞显著增敏（热增强比为2.07）。在37℃或41℃的FLDRI之前和/或之后在41℃孵育24小时不会增加辐射存活曲线的斜率，但会减小肩区。同样，在0.5Gy/h照射之前和/或之后在43℃加热30或60分钟也不会增强细胞敏感性。高剂量率（60Gy/h）照射后细胞的存活与照射期间的温度无关。在41℃预热24小时不会通过增加存活曲线的斜率使细胞对高剂量率照射增敏，尽管观察到肩区消失。在高剂量率照射之前在43℃加热30或60分钟的细胞增敏表现为经典的斜率改变。我们的结果表明，在FLDRI期间41℃加热可使细胞在长达36小时的暴露时间内对辐射诱导的杀伤显著增敏。在0.5Gy/h的FLDRI附近将9L细胞在41℃或43℃加热不会导致终末敏感性的额外增强，尽管观察到肩区改变。即使在41℃延长孵育期间产生了热耐受，上述同时加热仍会产生增敏作用。这些体外数据表明，在适度温度下同时进行长时间加热可大大增强低剂量率间质照射的细胞毒性作用，在临床应用中可能具有重要意义。
