Tokalov S V, Pieck S, Gutzeit H O
OncoRay-Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, University of Technology Dresden, Fetscherstrasse, Germany.
Cell Prolif. 2007 Feb;40(1):24-37. doi: 10.1111/j.1365-2184.2007.00421.x.
Both heat shock (HS) and ionizing radiation have an impact on the cell cycle and may induce cell cycle arrest or apoptosis. Mutations of the p53 gene are observed at a high frequency in human tumours and are recognized in about half of all human cancers. Sensitivity to radiation, heat and anticancer agents has been observed in p53(+/+) cells, but not in mutated or p53-deficient cells. Moreover, enhancement of radiosensitivity by HS has been observed in wild-type p53 cells but not in p53-deficient cells. The molecular mechanism of the differential cell response to HS or ionizing radiation is not yet understood.
Differences in cellular response to radiation (200 kV X-ray, 1, 2, 5 Gy) and HS (39 degrees C, 41 degrees C and 43 degrees C for 30 min) on cell cycle progression of cultures of human p53 mutant cells were investigated by flow cytometry. In addition, the effects of stressors used on the expression of several heat shock genes (HSP27, HSP60, HSP70, HSC70, HSP75, HSP78, HSP90) were studied by reverse transcriptase-polymerase chain reaction.
Yet, with respect to HSP gene expression, different stressors produced similar effects. Combination of HS and radiation treatment significantly induced the transcription of the HSP70 gene above the level induced by each stressor alone. Cell cycle analysis, however, revealed striking differences in prolonged dynamics of cell division in response to each stressor. Thus, p53 status could be a useful indicator in predictive assays for hyperthermia cancer treatment in combination with radiation and/or chemotherapy.
热休克（HS）和电离辐射均会对细胞周期产生影响，并可能诱导细胞周期停滞或凋亡。p53基因的突变在人类肿瘤中高频出现，约在所有人类癌症的一半中被发现。已观察到p53(+/+)细胞对辐射、热和抗癌药物敏感，而突变或p53缺陷细胞则不然。此外，在野生型p53细胞中观察到热休克增强了放射敏感性，而在p53缺陷细胞中则未观察到。细胞对热休克或电离辐射的不同反应的分子机制尚不清楚。
通过流式细胞术研究了人类p53突变细胞培养物在细胞周期进程中对辐射（200 kV X射线，1、2、5 Gy）和热休克（39℃、41℃和43℃处理30分钟）的细胞反应差异。此外，通过逆转录聚合酶链反应研究了所用应激源对几种热休克基因（HSP27、HSP60、HSP70、HSC70、HSP75、HSP78、HSP90）表达的影响。
然而，就热休克蛋白基因表达而言，不同的应激源产生了相似的效果。热休克和辐射处理的联合显著诱导了热休克蛋白70基因的转录，其水平高于单独每种应激源诱导的水平。然而，细胞周期分析显示，对每种应激源的反应中，细胞分裂的延长动态存在显著差异。因此，p53状态可能是热疗联合放疗和/或化疗治疗癌症的预测试验中的一个有用指标。
