Miller R C, Roizin-Towle L, Komatsu K, Richards M, Hall E J
Radiological Research Laboratories, College of Physicians & Surgeons of Columbia University, New York, NY 10032.
Int J Hyperthermia. 1989 Nov-Dec;5(6):697-705. doi: 10.3109/02656738909140494.
There is increasing concern for the oncogenic potential of agents used to treat cancer. Hyperthermia is one of the few modalities that does not, of itself, produce transformed foci in vitro. The adjuvant use of heat with X-rays or chemotherapy agents is an interesting approach to increasing the cell-killing potential while decreasing the oncogenicity of combined-modality therapy. Following a priming heat dose in C3H 10T1/2 cells, resistance to cell killing by a second heat dose develops and is maximal by 10 h. This is known as thermotolerance, and can be monitored by the appearance of proteins of specific molecular weight known as heat-shock proteins. By contrast, a priming heat dose does not confer resistance to killing by cis-platinum (cis-DDP). Indeed, heat potentiates the cytotoxicity due to cis-DDP. The interaction is greatest if heat and drug are applied simultaneously, but is still substantial if the drug is applied many hours after heating. The loss of interaction between heat and cis-DDP occurs slowly, but by 48 h, heat and drug act independently. Thermotolerant cells are less sensitive to the induction of transformation by X-rays than previously unheated cells. On the other hand, 48 h after a heat exposure, when cells have regained their normal sensitivity to killing by cis-DDP, their sensitivity to the induction of transformation by cis-DDP has also returned to normal.
人们越来越关注用于治疗癌症的药物的致癌潜力。热疗是少数几种本身在体外不会产生转化灶的治疗方式之一。将热与X射线或化疗药物联合使用是一种有趣的方法，可在降低联合治疗致癌性的同时提高细胞杀伤潜力。在C3H 10T1/2细胞中给予预适应热剂量后，细胞对第二次热剂量的杀伤产生抗性，并在10小时时达到最大值。这被称为热耐受，可通过特定分子量的蛋白质（即热休克蛋白）的出现来监测。相比之下，预适应热剂量不会使细胞对顺铂（cis-DDP）的杀伤产生抗性。实际上，热会增强顺铂的细胞毒性。如果热和药物同时应用，这种相互作用最大，但如果在加热后数小时应用药物，这种相互作用仍然很大。热与顺铂之间的相互作用丧失缓慢，但到48小时时，热和药物的作用相互独立。热耐受细胞对X射线诱导的转化比未加热的细胞更不敏感。另一方面，热暴露48小时后，当细胞恢复对顺铂杀伤的正常敏感性时，它们对顺铂诱导转化的敏感性也恢复到正常水平。
