Erythropoietin restores the anemia-induced reduction in radiosensitivity of experimental human tumors in nude mice

• Published in: International journal of radiation oncology, biology, physics Vol. 55; no. 5; pp. 1358 - 1362
• Main Authors: Stüben, Georg, Pöttgen, Christoph, Knühmann, Kai, Schmidt, Kai, Stuschke, Martin, Thews, Oliver, Vaupel, Peter
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.04.2003; Elsevier
• Subjects: Anemia; Anemia - complications; Anemia - drug therapy; Anemia - metabolism; Animals; Biological and medical sciences; Cell Hypoxia; Dose Fractionation, Radiation; Drug Evaluation, Preclinical; Erythropoietin; Erythropoietin - pharmacology; Erythropoietin - therapeutic use; Hemoglobins - analysis; Human sarcoma xenografts; Humans; Hypoxia; Medical sciences; Mice; Mice, Nude; Neoplasm Transplantation; Other treatments; Radiation Injuries, Experimental - complications; Radiation Injuries, Experimental - drug therapy; Radiation Injuries, Experimental - metabolism; Radiation Tolerance - drug effects; Radiosensitivity; Recombinant Proteins; Sarcoma - complications; Sarcoma - metabolism; Sarcoma - radiotherapy; Transplantation, Heterologous; Treatment. General aspects; Tumors; Whole-Body Irradiation - adverse effects; Hypoxia; Human sarcoma xenografts; Radiosensitivity; Erythropoietin; Anemia; Human; Animal model; Treatment efficiency; Hemopathy; Case control study; Malignant tumor; Experimental study; Heterograft; Radiotherapy; Animal; Radiation injury; Complication
• ISSN: 0360-3016; 1879-355X
• 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 × 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.