Stüben Georg, Pöttgen Christoph, Knühmann Kai, Schmidt Kai, Stuschke Martin, Thews Oliver, Vaupel Peter
Department of Radiotherapy, West German Tumor Centre, Universitätsklinikum, Essen, Germany.
Int J Radiat Oncol Biol Phys. 2003 Apr 1;55(5):1358-62. doi: 10.1016/s0360-3016(03)00012-9.
The effect of recombinant human erythropoietin (rhEPO) on the radiosensitivity of human tumor xenografts growing in anemic and nonanemic nude mice was studied.
Anemia was induced by total body irradiation ([TBI], 2 x 4 Gy) of mice before tumor implantation into the subcutis of the hind leg. The development of anemia was prevented by rhEPO (750 U/kg s.c.) given 3 times weekly starting 2 weeks before TBI. Fourteen days after fractionated TBI (tumor volume of approx. 40 mm(3)), single-dose irradiation of the tumor with varying doses was performed so that in full dose-response relationship for the probability of tumor cure was obtained.
Radiation-induced anemia (hemoglobin concentration [cHb] = 9.9 g/dl) led to a reduced radiosensitivity compared to controls [49.4 vs. 40.1 Gy radiation dose to control 50% of the tumors (TCD50)]. Upon rhEPO treatment for anemia prevention (cHb = 13.3 g/dl), the TCD50 was 39.8 Gy, illustrating restored radiosensitivity compared to anemic mice.
These data provide further experimental evidence for restored radiosensitivity upon prevention of anemia with rhEPO.
研究重组人促红细胞生成素(rhEPO)对贫血和非贫血裸鼠体内生长的人肿瘤异种移植瘤放射敏感性的影响。
在将肿瘤植入小鼠后腿皮下之前,通过全身照射(TBI,2×4 Gy)诱导小鼠贫血。在TBI前2周开始,每周3次皮下注射rhEPO(750 U/kg)以预防贫血的发生。在分次TBI 14天后(肿瘤体积约为40 mm³),对肿瘤进行不同剂量的单次照射,从而获得完整的肿瘤治愈概率剂量反应关系。
与对照组相比,辐射诱导的贫血(血红蛋白浓度[cHb]=9.9 g/dl)导致放射敏感性降低[对照组50%肿瘤的辐射剂量(TCD50)为49.4 Gy,贫血组为40.1 Gy]。在rhEPO治疗预防贫血后(cHb = 13.3 g/dl),TCD50为39.8 Gy,说明与贫血小鼠相比放射敏感性恢复。
这些数据为rhEPO预防贫血后放射敏感性恢复提供了进一步的实验证据。