Mini E, Dombrowski J, Moroson B A, Bertino J R
Eur J Cancer Clin Oncol. 1986 Aug;22(8):927-34. doi: 10.1016/0277-5379(86)90058-1.
The cytotoxic effects of 5-fluorouracil (FUra), hyperthermia, and the combination of these treatments were examined in a human T-lymphoblast cell line, CCRF-CEM. Simultaneous exposure of exponentially growing CCRF-CEM cells to hyperthermia (39 and 42 degrees C) and FUra (10, 50, and 100 microM) for 1 or 2 hr resulted in subadditive or additive cell kill. When CCRF-CEM cells were exposed to these agents in sequence (hyperthermia----FUra and FUra----hyperthermia) for 1 and 2 hr duration additive cell kill was also observed. Enhanced cytotoxic effects were observed when a longer exposure (4 and 8 hr) to FUra (100 microM) followed heat (42 degrees C for 1 and 2 hr). Heat exposure (42 degrees C, 1 and 2 hr) induced a rapid decrease in the synthesis of DNA of CCRF-CEM cells, followed by a rebound increase at 12 hr and a new decrease at 24 hr. Flow cytometry demonstrated an accumulation of cells in the S phase at 12 hr after heat exposure, followed by a marked increase of the G + M population (maximum at 24 hr). The exposure time, and the sequence of administration of hyperthermia and FUra were critical determinants of cytotoxicity in this in vitro system and might constitute important variables of treatment when these two agents are used clinically.
在人T淋巴母细胞系CCRF - CEM中检测了5 - 氟尿嘧啶（FUra）、热疗以及这两种治疗方法联合使用的细胞毒性作用。将指数生长期的CCRF - CEM细胞同时暴露于热疗（39℃和42℃）和FUra（10、50和100微摩尔）1或2小时，导致细胞杀伤呈次相加或相加作用。当CCRF - CEM细胞依次暴露于这些药物（热疗→FUra和FUra→热疗）1和2小时时，也观察到相加的细胞杀伤作用。当在热疗（42℃，1和2小时）后更长时间（4和8小时）暴露于FUra（100微摩尔）时，观察到细胞毒性增强。热暴露（42℃，1和2小时）导致CCRF - CEM细胞DNA合成迅速减少，随后在12小时出现反弹增加，在24小时再次减少。流式细胞术显示热暴露后12小时细胞在S期积累，随后G + M群体显著增加（在24小时达到最大值）。在这个体外系统中，暴露时间以及热疗和FUra的给药顺序是细胞毒性的关键决定因素，并且在临床使用这两种药物时可能构成治疗的重要变量。
