The effects of 5-fluorouracil on hematopoiesis: Studies of murine megakaryocyte-CFC, granulocyte-macrophage-CFC, and peripheral blood cell levels

The effect of 5-fluorouracil (5-FU) on megakaryocytopoiesis in mice was studied with assays of megakaryocyte colony-forming cells (Meg-CFC) in bone marrow and spleen and simultaneous determinations of peripheral blood counts, after a single intraperitoneal dose (150 mg/kg) of 5-FU. Although only moderate thrombocytopenia (platelet count 40% of control values) occurred at 7 days following administration of 5-FU, sustained rebound thrombocytosis (platelets 200-250% of control values) was observed from days 11 to 17. No rebound leukocytosis was detected despite comparable initial leukopenia. Megakaryocyte colony-forming cells (Meg-CFC) in bone marrow and spleen were decreased for 2 and 5 days, respectively, after administration of 5-FU. Subsequently, there was a prolonged rebound increase in the total number of Meg-CFC in the spleen from days 11 to 17 after 5-FU, a phenomenon which did not occur with Meg-CFC derived from bone marrow. Granulocyte-macrophage colony-forming cells (GM-CFC) in bone marrow and spleen exhibited alterations which were similar to those of Meg-CFC, indicating similar sensitivities of GM-CFC and Meg-CFC to 5-FU. Normal feedback mechanisms with control platelet levels are perturbed for almost 3 wk after administration of 5-FU. The simultaneous occurrence of maximal thrombocytosis and increased splenic Meg-CFC suggests that increased platelet production after 5-FU is associated with concomitant stimulation of the megakaryocyte progenitor compartment in the mouse spleen. However, the concurrence of thrombocytosis and increased splenic Meg-CFC indicates that elevated levels of Meg-CFC did not initiate the period of thrombocytosis.