Konings A W, Penninga P
Int J Radiat Biol Relat Stud Phys Chem Med. 1985 Sep;48(3):409-22. doi: 10.1080/09553008514551411.
Heating of Ehrlich ascites tumour (EAT) cells and mouse fibroblast LM cells to 43 or 44 degrees C respectively, results in an increased level of reduced glutathione (GSH). The maximum elevation in GSH was to 140 per cent for LM cells and to 120 per cent for EAT cells. No increase of GSH in EAT cells was observed after heating at 44 degrees C. LM cells were treated with diethylmaleate (DEM) and the EAT cells with buthionine-sulphoximine (BSO) at non-toxic doses to deplete the levels of GSH. No effect on thermosensitivity or on the development of thermotolerance was observed when the DEM and BSO treatments were chosen such that the lowering of GSH was just down to the level of detection (about 5 per cent of control). When higher concentrations of DEM were used, thermal sensitization was observed. The activity of the pentose phosphate pathway (PPP) was also investigated because of its importance in supplying NADPH for the regeneration of GSH from GSSG and for the endogenous production of polyols. Hyperthermia was found to enhance markedly the flux of glucose through the PPP. While the DEM treatment inhibited glucose oxidation through the PPP, BSO addition to the cells resulted in a slightly increased activity of the PPP. The PPP activity of thermotolerant cells was lower (fibroblasts) or hardly affected (EAT cells) compared to control cells. The extent of PPP activation by hyperthermia was comparable for thermotolerant and control cells. For the two cell lines studied neither a high level of GSH nor an active PPP is a prerequisite for the development of thermotolerance.
将艾氏腹水瘤（EAT）细胞和小鼠成纤维细胞LM细胞分别加热至43或44摄氏度，会导致还原型谷胱甘肽（GSH）水平升高。LM细胞中GSH的最大升高幅度为140%，EAT细胞为120%。在44摄氏度加热后，未观察到EAT细胞中GSH增加。用无毒剂量的马来酸二乙酯（DEM）处理LM细胞，用丁硫氨酸亚砜胺（BSO）处理EAT细胞，以耗尽GSH水平。当选择DEM和BSO处理使GSH降低至刚好检测水平（约为对照的5%）时，未观察到对热敏感性或热耐受性发展有影响。当使用更高浓度的DEM时，观察到热敏化。还研究了磷酸戊糖途径（PPP）的活性，因为它在为从氧化型谷胱甘肽（GSSG）再生GSH以及内源性产生多元醇提供烟酰胺腺嘌呤二核苷酸磷酸（NADPH）方面具有重要性。发现热疗可显著增强葡萄糖通过PPP的通量。虽然DEM处理抑制了葡萄糖通过PPP的氧化，但向细胞中添加BSO导致PPP活性略有增加。与对照细胞相比，热耐受细胞的PPP活性较低（成纤维细胞）或几乎不受影响（EAT细胞）。热疗对PPP的激活程度在热耐受细胞和对照细胞中相当。对于所研究的两种细胞系，高水平的GSH或活跃的PPP都不是热耐受性发展的先决条件。
