Hydroxyurea, a cytotoxic agent that kills cells in DNA synthesis, was used to study the relationship between erythropoietin and the generative cycle of the immediate erythroid precursor cell. When OHU and EP were administered simultaneously to hypertransfused mice, the resultant erythroid response was diminished relative to EP treated controls. OHU given at intervals after EP resulted in a progressively greater diminution of erythroid response.
From these studies, then, we would suggest that in the suppressed animal the committed stem cell compartment is in cycle but with a prolonged G1. After EP there is a shortening of the generation time and an increase in the rate of turnover of the committed stem cells. The data also indicate that cells in cycle are differentiated into the pronormoblast compartment. It further may be suggested that erythropoietin is effective throughout the bulk of the generative cycle although it seems unlikely that differentiation is accomplished during the mitotic phase. Whether erythropoietin must be present in both G1 and S as suggested by Kretchmar cannot be answered by the present studies. The data also indicate that cells of the pluripotential compartment are normally in G0 or perhaps a prolonged G1. Damage to the committed compartment appears to be in part repaired by the influx of cells from the pluripotential compartment.