Pathogenesis of anemia in rats with Walker 256 carcinosarcoma

The purpose of this study was to further clarify the pathophysiology of anemia in malignancy. To accomplish this end a total of 210 normal or splenectomized rats with or without the solid form of Walker 256 carcinosarcoma was studied. In vivo studies demonstrated that in stage I cancer (tumor weight less than 10% of body weight) a slightly shortened red cell survival resulted in a mild degree of anemia. With increasing tumor size, 51Cr red cells mass decreased further, in spite of extramedullary erythropoiesis and a slightly increased incorporation transferrin-bound iron into red cells. Splenectomized rats with stage II cancer developed a more profound degree of anemia associated with a significantly decreased incorporation of 59Fe into red cells. Marrow cell culture studies demonstrated that heme synthesis in response to erythropoietin in stage I cancer was not significantly different from normal, but in rats with stage II cancer (tumor weight greater than 10% of body weight) heme synthesis in response to erythropoietin was markedly decreased. In vitro studies demonstrated that plasma erythropoietin levels were appropriately increased in most rats with transplanted malignancy. These studies indicate that bone marrow heme synthesis in response to erythropoietin is impaired in rats with the anemia of advanced malignancy.