Can erythropoietin improve tumor oxygenation?

Abstract

Tumor growth, oxygenation and radiosensitivity were investigated in a series of studies in which anemia was induced in rats either by the development of a hemorrhagic ascites or by a single dose of carboplatin, which resulted in reductions in the hemoglobin concentration of 30%. The development of both the tumor- and chemotherapy-induced forms of anemia could be prevented by the s. c. administration of recombinant human erythropoietin (rhEPO; 1000 IU/kg, 3 times per week over 14 days). Seven days before pO2 measurements, DS-sarcomas were implanted s. c. on the hind foot dorsum. With both anemia models, tumor growth did not differ between anemic animals and animals treated with rhEPO. Tumor oxygenation was measured polarographically using O2-sensitive needle electrodes and pO2 histography. In anemic animals, tumor oxygenation was poorer compared to untreated controls. The reduction could be partially reversed by rhEPO treatment, but not fully compensated. These findings suggested that rhEPO treatment can improve tumor oxygenation by increasing the O2 availability to tumor tissue. Further experiments therefore assessed the possibility of enhancing the efficacy of a single radiation dose (10 Gy) by rhEPO treatment of anemic animals. While anemic animals showed decreased radiosensitivity, prevention of anemia by rhEPO treatment resulted in a significant increase in tumor radiosensitivity, although again a full recovery to radiosensitivity levels found in non-anemic animals was not achieved.