Computerized histographic characterization of changes in tissue pO2 induced by erythropoietin

Anemia associated with malignancy is a common clinical problem, and has a negative effect on oxygen delivery and, therefore, response of tumors to radiotherapy. Erythropoietin (EPO) has been shown to increase the hematocrit of rodents when administered subcutaneously. The objectives of this study were to measure tumor and normal tissue pO2 with computerized pO2 histography, to characterize the change in rodent hematocrit with EPO administration, and to assess the capacity of pO2 histography to measure changes in tumor pO2 during growth, with or without EPO administration. Ten C3H mice were implanted with SCCVII tumors and after three weeks of tumor growth, EPO (1500 IU/kg/day) was administered for two weeks. Tumor and subcutaneous (SQ) measurements were made weekly with an Eppendorf pO2 histograph and hematocrits were obtained concomitantly. Eight C3H/SCCVII mice, which received no EPO and underwent similar measurements, served as controls. The hematocrits of the control mice dropped progressively from 42.0 to 23.0% during the two week period. There was a corresponding fall in both the SQ and tumor mean pO2 (55.6 to 40.3 mm Hg, and 19.9 to 10.0 mm Hg, respectively). In the treated group, the hematocrits remained stable (38.0 to 43.1%) as did the mean pO2 of the SQ (46.1 to 54.3 mm Hg) and the tumor (11.1 to 11.3 mm Hg). These data lend support to the value of EPO in reversing the anemia associated with malignancy and suggest a role of pO2 histography in monitoring the beneficial effects of EPO therapy.