Polycythemia in Hepatocellular Carcinoma-Bearing B6C3F1 Mice

Secondary polycythemia was observed in hepatocellular carcinoma-bearing B6C3F1 mice which were used as control group animals in 2-year carcinogenicity studies. Statistically significant increases in erythrocyte count, hematocrit value, hemoglobin concentration, and absolute reticulocyte count were noted in the peripheral blood of hepatocellular carcinoma-bearing mice as compared with non-tumor-bearing mice. A decrease in mean corpuscular volume and mean corpuscular hemoglobin value was also noted in hepatocellular carcinoma-bearing mice. Mean corpuscular hemoglobin concentration and relative reticulocyte count in hepatocellular carcinoma-bearing mice were comparable to those in non-tumor-bearing mice. In addition, the plasma erythropoietin level in hepatocellular carcinoma-bearing mice was significantly higher than that in hepatocellular adenoma-bearing mice and that in non-tumor-bearing mice. Therefore, the hematological changes observed in hepatocellular carcinoma-bearing mice were diagnosed as secondary polycythemia. At necropsy, the spleen in hepatocellular carcinoma-bearing mice was dark-red and enlarged 2 to 4 times compared with that in non-tumor-bearing mice. Histopathologic examination revealed proliferation of the erythroid cells and megakaryocytes in the spleen and bone marrow in hepatocellular carcinoma-bearing mice, suggesting an increase in erythropoietic activity. These findings indicate that increased levels of plasma erythropoietin in hepatocellular carcinoma-bearing mice stimulate erythropoiesis in the hematopoietic organs and result in proliferation of microcytic and hypochromic erythrocytes. Possible mechanisms for the induction of secondary polycythemia in hepatocellular carcinoma-bearing mice are discussed.