The effects of a single dose (150 mg/kg) of 5-fluorouracil on mature erythroid and erythropoietic and multipotential in vitro precursor populations in the bone marrow and spleen and circulating biologically (erythroid colony forming unit [CFU-E] assay) and immunologically active (enzyme-linked immunosorbent assay) erythropoietin (Epo) are described. All mature erythroid (reticulocytes, erythrocytes) and in vitro erythropoietic precursors (CFU-E, erythroid burst-forming unit [BFU-E]) are severely reduced, if not eradicated. Transient repopulation of the pure BFU-E and CFU-E populations on days 6 and 7, respectively, produces a marked reticulocytosis after day 9. Circulating Epo increases to above normal values by day 2. However, whereas biologically active Epo remains constant at this level until day 9, immunologically active Epo continually increases; by day 12, however, both assays detect circulating Epo levels of about 400 mU/mL. In vitro multipotential stem cells (BFU-E mix) are reduced to 32% on day 1, 7.6% on day 2, and return to normal values between days 4 and 5. The survival and repopulation kinetics of the BFU-E mix imply a stem cell population more mature than the high proliferative potential colony-forming cells. However, the BFU-E mix may be responsible for erythropoiesis repopulating ability.

Using the technique for erythroid colony formation in vitro, bone marrow and spleen cells from NMRI mice were studied after Rauscher virus (RLV) infection. There was a substantial decrease in CFUE concentrations during the first days after infection, this being more pronounced in the marrow than in the spleen. In the marrow values gradually return to and are maintained at control levels, while in the spleen a 40-50-fold increase is seen between days 8 and 18. In normal and RLV infected animals the same dose dependence of CFUE growth for erythropoietin was seen. For normal and RLV infected cells in the absence of erythropoietin there were only very few background colonies. In exhypoxic plethoric mice the increase in CFUE concentration seen in normal mice in the spleen, is delayed by 2-3 days.