BLOOD-FLOW, OXYGENATION, AND BIOENERGETIC STATUS OF TUMORS AFTER ERYTHROPOIETIN TREATMENT IN NORMAL AND ANEMIC RATS

Growth, blood flow, oxygenation, and bioenergetic status of experiment al tumors were investigated in normal (control) and anemic animals aft er administration of recombinant human erythropoietin (rhEPO). DS sarc omas were implanted s.c. onto the hind foot dorsum of Sprague-Dawley r ats. Tumor-associated anemia was induced by the development of an i.p. hemorrhagic ascites. rhEPO (1000 IU/kg) mas administered s.c. three t imes per week over 14 days, after which it was found to have significa ntly increased hematocrit values in both normal and anemic animals. Tu mor growth in anemic animals was slower than in normal animals, and rh EPO administration did not influence tumor growth in either group. Tum or blood flow in anemic animals was lower than in control animals and was only increased in larger tumors in animals in which anemia mas pre vented by prophylactic rhEPO application. Tumor oxygenation, determine d using polarographic needle electrodes and oxygen partial pressure hi stography, mas poorer in anemic animals than in normal animals. This r eduction could be reversed partially, but not compensated fully by rhE PO treatment in smaller tumors (less than or equal to 1.4 ml). These c hanges suggest that rhEPO, by improving tumor oxygenation, may increas e the efficacy of standard radiotherapy in anemic animals and may be o f use in anemic tumor patients in whom the success of radiotherapy or O-2-dependent chemotherapy might be limited by tumor hypoxia.