Krag D N, Theon A P, Gan L
Department of Surgery, University of California, Davis, Sacramento 95817.
Cancer Res. 1990 Apr 15;50(8):2385-9.
The effect of elevated temperature on cytotoxicity of rhodamine 123 (R123) was tested in vitro on B16 mouse melanoma cells. Simultaneous 1-h exposure to R123 and hyperthermia (43 degrees C for 1 h) resulted in marked enhancement of R123 cytotoxicity. Thermal enhancement of R123 cytotoxicity occurred at temperatures as low as 38 degrees C. Heat treatment (43 degrees C for 1 h) given immediately before or after R123 exposure (37 degrees C for 1 h) yielded no significant increase in cytotoxicity over that expected for strict additivity. The effects of heat on two mechanisms reported to be associated with R123 cytotoxicity were evaluated: (a) target inactivation by R123; and (b) R123 intracellular accumulation. Hyperthermia caused an increased rate of target inactivation by R123 and also caused an increased net intracellular accumulation of R123. This indicates that at least two mechanisms are responsible for the synergistic cytotoxicity of R123 and hyperthermia.
在体外对B16小鼠黑色素瘤细胞测试了高温对罗丹明123（R123）细胞毒性的影响。同时将R123与热疗（43℃，1小时）一起暴露1小时，导致R123细胞毒性显著增强。R123细胞毒性的热增强在低至38℃的温度下就会发生。在R123暴露（37℃，1小时）之前或之后立即进行热处理（43℃，1小时），其细胞毒性的增加并不比严格相加预期的显著。评估了热对两种据报道与R123细胞毒性相关机制的影响：（a）R123导致的靶点失活；（b）R123在细胞内的积累。热疗导致R123使靶点失活的速率增加，也导致R123在细胞内的净积累增加。这表明至少有两种机制导致了R123与热疗的协同细胞毒性。
