Impact of anemia prevention by recombinant human erythropoietin on the sensitivity of xenografted glioblastomas to fractionated irradiation.
BACKGROUND
Pronounced oxygen deficiency in tumors which might be caused by a diminished oxygen transport capacity of the blood (e.g., in anemia) reduces the efficacy of ionizing radiation. The aim of this study was to analyze whether anemia prevention by recombinant human erythropoietin (rHuEPO) affects the radiosensitivity of human glioblastoma xenografts during fractionated irradiation.


METHODS
Anemia was induced by total body irradiation (TBI, 2 x 4 Gy) of mice prior to tumor implantation into the subcuts of the hind leg. In one experimental group, the development of anemia was prevented by rHuEPO (750 U/kg s.c.) given three times weekly starting 10 days prior to TBI. 13 days after tumor implantation (tumor volume approx. 40 mm3), fractionated irradiation (4 x 7 Gy, one daily fraction) of the glioblastomas was performed resulting in a growth delay with subsequent regrowth of the tumors.


RESULTS
Compared to nonanemic control animals (hemoglobin concentration cHb = 14.7 g/dl), the growth delay in anemic mice (cHb = 9.9 g/dl) was significantly shorter (49 +/- 5 days vs. 79 +/- 4 days to reach four times the initial tumor volume) upon fractionated radiation. The prevention of anemia by rHuEPO treatment (cHb = 13.3 g/dl) resulted in a significantly prolonged growth delay (61 +/- 5 days) compared to the anemia group, even though the growth inhibition found in control animals was not completely achieved.


CONCLUSIONS
These data indicate that moderate anemia significantly reduces the efficacy of radiotherapy. Prevention of anemia with rHuEPO partially restores the radiosensitivity of xenografted glioblastomas to fractionated irradiation.
Stüben
Georg
G
West German Tumor Center, Department of Radiotherapy, University Hospital Essen, Germany. georg.stueben@uni-essen.de
Thews
Oliver
O
Pöttgen
Christoph
C
Knühmann
Kai
K
Sack
Horst
H
Stuschke
Martin
M
Vaupel
Peter
P
D000740:Anemia / Q000150:complications / Q000209:etiology / Q000517:prevention & control*; D000818:Animals; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D019583:Dose Fractionation, Radiation; D004921:Erythropoietin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005909:Glioblastoma / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011836:Radiation Tolerance / Q000187:drug effects; D011879:Radiotherapy Dosage; D011994:Recombinant Proteins; D013997:Time Factors; D014183:Transplantation, Heterologous; D014916:Whole-Body Irradiation
D011994:Recombinant Proteins; D004921:Erythropoietin