Raaphorst G P, Feeley M M, Chu G L, Dewey W C
Ottawa Regional Cancer Center, Ontario, Canada.
Int J Hyperthermia. 1993 Mar-Apr;9(2):303-12. doi: 10.3109/02656739309022543.
The hyperthermia response of two human glioma cells lines (87MG and 373MG) was compared to the CHO cell line for cell killing and DNA polymerase inactivation. Glioma cells were found to be more thermally resistant than CHO cells over a temperature range of 41-46 degrees C. Inactivation of polymerase alpha and beta by hyperthermia was also more resistant in glioma cells than in CHO cells. The relative order of resistance for both killing and polymerase inactivation was 373MG > 87MG > CHO. While polymerase inactivation correlated with cell killing at high thermal doses, such correlation at low doses was absent; i.e. thermal killing was characterized by survival curves with shoulders while polymerase inactivation was not. Thus at low thermal doses the mechanism of thermal cell killing is probably not related to the degree of polymerase inactivation. Arrhenius analysis of the survival data showed that the inactivation energy for the glioma cells was 133-135 kcal/mol. The inactivation energies of alpha and beta polymerase were also evaluated and were 102-104 and 140-146 kcal/mol, respectively. Further analysis of the temperature-time relationship of hyperthermia treatment resulting in 50% cell kill showed the degree of polymerase beta inactivation to be a good indicator of thermal dose.
比较了两种人类胶质瘤细胞系（87MG和373MG）与CHO细胞系在细胞杀伤和DNA聚合酶失活方面的热疗反应。发现在41-46摄氏度的温度范围内，胶质瘤细胞比CHO细胞具有更高的耐热性。热疗导致的聚合酶α和β的失活在胶质瘤细胞中也比在CHO细胞中更具抗性。在细胞杀伤和聚合酶失活方面，抗性的相对顺序为373MG > 87MG > CHO。虽然在高热剂量下聚合酶失活与细胞杀伤相关，但在低剂量下不存在这种相关性；即热杀伤的特征是存活曲线有肩部，而聚合酶失活则没有。因此，在低热剂量下，热细胞杀伤的机制可能与聚合酶失活的程度无关。对存活数据的阿伦尼乌斯分析表明，胶质瘤细胞的失活能量为133-135千卡/摩尔。还评估了α和β聚合酶的失活能量，分别为102-104千卡/摩尔和140-146千卡/摩尔。对导致50%细胞杀伤的热疗温度-时间关系的进一步分析表明，聚合酶β失活的程度是热剂量的良好指标。
