Erythropoietin restores the anemia-induced reduction in radiosensitivity of experimental human tumors in nude mice.
OBJECTIVE
The effect of recombinant human erythropoietin (rhEPO) on the radiosensitivity of human tumor xenografts growing in anemic and nonanemic nude mice was studied.


METHODS
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.


RESULTS
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.


CONCLUSIONS
These data provide further experimental evidence for restored radiosensitivity upon prevention of anemia with rhEPO.
Stüben
Georg
G
Department of Radiotherapy, West German Tumor Centre, Universitätsklinikum, Essen, Germany. georg.sueben@uni-essen.de
Pöttgen
Christoph
C
Knühmann
Kai
K
Schmidt
Kai
K
Stuschke
Martin
M
Thews
Oliver
O
Vaupel
Peter
P
D000740:Anemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D015687:Cell Hypoxia; D019583:Dose Fractionation, Radiation; D004353:Drug Evaluation, Preclinical; D004921:Erythropoietin / Q000494:pharmacology* / Q000627:therapeutic use; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011833:Radiation Injuries, Experimental / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D011836:Radiation Tolerance / Q000187:drug effects*; D011994:Recombinant Proteins; D012509:Sarcoma / Q000150:complications / Q000378:metabolism / Q000532:radiotherapy*; D014183:Transplantation, Heterologous; D014916:Whole-Body Irradiation / Q000009:adverse effects
D006454:Hemoglobins; D011994:Recombinant Proteins; D004921:Erythropoietin