Chemical-Induced Erythrocytosis in Wistar Rats: Assessment as a Model for Human Polycythemia

摘要

Polycythemia is a hematological disease characterized by erythrocytosis and occasionally leukocytosis. The purpose of this study was to reproduce and characterize a polycythemic condition produced in a closed colony of Wistar rats. Following transplacental exposure to methyl-mercury, ethylurea, and sodium nitrite, the rats developed up to 41% incidence of polycythemia. Clinical signs of polycythemia developed in offspring from all methylmercury-treated groups, with the highest incidence seen in groups exposed to all three chemicals. Most cases appeared at 8 weeks of age with fewer cases between 3 and 9 months of age. Chronic methylmercury treatment of the dams was essential, and butylnitrosourea plus methylmercury was also capable of inducing the disease. Hematocris in afflicted animals ranged from 60 to 84%. Blood cell morphology and differential counts were generally normal. The red cell mass was significantly elevated which was indicative of absolute erythrocytosis. Marrow cell culture studies and elevated erythropoietin levels in diseased rats were diagnostic of secondary polycythemia; however, no apparent secondary causes were detected. Erythrocytes from polycythemic rats were previously found to have an increased affinity for oxygen, but no hemoglobin abnormalities were initially detected. Presently, this disease offers considerable potential for furthering the knowledge of hematopoiesis and may eventually serve as a model for secondary polycythemia in humans.