Enhanced cell killing by bleomycin and 43 degrees hyperthermia and the inhibition of recovery from potentially lethal damage.
Enhanced cell killing by bleomycin and 43 degrees hyperthermia and the inhibition of recovery from potentially lethal damage.
复制标题
博来霉素和 43 度高温可增强细胞杀伤力，并抑制潜在致命损伤的恢复。
作者：
J. Braun;G. Hahn
在“不进食”的单层培养的中国仓鼠细胞中研究了高温对博莱霉素（BLEO）毒性和修复的影响。在同时暴露于BLEO和43度的情况下观察到毒性的协同作用。例如，当细胞在43度下暴露于BLEO（40 μ g/ml）1小时时，存活率降低至4 × 10 - 5;单独地，高温和37度BLEO暴露各自导致20%的存活率。在药物暴露于37度之前在43度加热也产生了大量的致敏作用，表明主要的致敏作用涉及细胞损伤，而不是药物作用速率的增加; 41度仅对BLEO产生了适度的细胞致敏作用，并且在药物暴露之前加热的细胞中没有保留这种作用。与37度相比，在43度下未观察到[14 C]BLEO摄取增加，因此细胞毒性增加与BLEO细胞渗透性的总体变化无关，尽管不能排除特定敏感靶点的药物可用性增加。对不同43度BLEO方案后的修复动力学研究表明，大多数维持潜在致命损伤的细胞迅速恢复。然而，43度高温抑制了这种恢复，随着43度暴露持续时间的增加，潜在致命损伤的固定增强。由于在体内观察到的BLEO损伤的实质性修复，热疗作为BLEO治疗的辅助治疗的可能有用性进行了讨论。
The effect of hyperthermia on bleomycin (BLEO) toxicity and repair was studied in "unfed" monolayer cultures of Chinese hamster cells. Synergy of toxicities was observed with simultaneous exposure to BLEO and 43 degrees. For example, when cells were exposed for 1 hr to BLEO (40 mug/ml) at 43 degrees, survival was reduced to 4 X 10(-5); separately, hyperthermia and 37 degrees BLEO exposure each resulted in a survival of 20%. Heating at 43 degrees prior to drug exposure at 37 degrees also produced substantial sensitization, indicating that the primary sensitizing effect involved cell damage rather than an increased rate of drug action; 41 degrees produced only modest cell sensitization to BLEO and the effect was not retained in cells heated prior to drug exposure. No increase in [14C]BLEO uptake was observed at 43 degrees over than at 37 degrees, and thus the increased cytotoxicity was not correlated with a gross change in cell permeability to BLEO, although increased drug availability to particular sensitive targets could not be ruled out. Studies of the repair kinetics after different 43 degrees BLEO protocols demonstrated that most of the cells sustaining potentially lethal damage rapidly recovered. However, 43 degrees hyperthermia inhibited this recovery and, with increasing durations of 43 degrees exposure, the fixation of potentially lethal damage was enhanced. Because of the substantial repair of BLEO damage observed in vivo, the possible usefulness of hyperthermia as an adjunct to BLEO therapy is discussed.