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

Int J Radiat Oncol Biol Phys. 2003 Apr 1;55(5):1358-62. doi: 10.1016/s0360-3016(03)00012-9.

Abstract

Purpose: The effect of recombinant human erythropoietin (rhEPO) on the radiosensitivity of human tumor xenografts growing in anemic and nonanemic nude mice was studied.

Methods and materials: 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.

Conclusion: These data provide further experimental evidence for restored radiosensitivity upon prevention of anemia with rhEPO.

MeSH terms

  • Anemia / complications
  • Anemia / drug therapy*
  • Anemia / metabolism
  • Animals
  • Cell Hypoxia
  • Dose Fractionation, Radiation
  • Drug Evaluation, Preclinical
  • Erythropoietin / pharmacology*
  • Erythropoietin / therapeutic use
  • Hemoglobins / analysis
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Radiation Injuries, Experimental / complications
  • Radiation Injuries, Experimental / drug therapy*
  • Radiation Injuries, Experimental / metabolism
  • Radiation Tolerance / drug effects*
  • Recombinant Proteins
  • Sarcoma / complications
  • Sarcoma / metabolism
  • Sarcoma / radiotherapy*
  • Transplantation, Heterologous
  • Whole-Body Irradiation* / adverse effects

Substances

  • Hemoglobins
  • Recombinant Proteins
  • Erythropoietin