Dose-response and time-response study of erythrocytosis in rats after intrarenal injection of nickel subsulfide.

Erythrocytosis was induced in Fischer rats by intrarenal (ir) injection of nickel subsulfide (Ni3S2) in dosages ranging from 0.6 to 10 mg per rat. Measurements of blood packed cell volume (PCV) became increased by one month after ir injection of Ni3S2; reached maximum values at approximately two months; and gradually returned to control values by seven months. The duration and magnitude of erythrocytosis were related to the dosage of Ni3S2. Increases in hemoglobin concentrations and erythrocyte counts (RBC) in Ni3S2-treated rats were consistently proportional to blood PCV values. Blood hemoglobin concentration was 24.9 +/- 1.2 g per dl at two months after bilateral ir injection of Ni3S2 (10 MG PER RAT), VERSUs 15.8 +/- 0.5 g per dl in saline-injected controls (P less than 0.001). No significant changes occurred in leukocyte or platelet counts of Ni3S2-treated rats. Autopsy of rats killed two months after ir injection of Ni3S2 showed marked erythroid hyperplasia of bone marrow and fibrotic needle tracts in renal parenchyma with localized deposits of particles of Ni3S2. In contrast to the erythrocytosis induced by ir injection of Ni3S2, administration of Ni3S2 by intramuscular (im) injection (10 mg per rat) had no significant effect upon blood PCV, RBC or hemoglobin values or upon morphology of bone marrow.