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  • Title: The autonomous release of erythropoietic inhibition during long-term in vivo administration of actinomycin D.
    Author: Rich IN, Kubanek B.
    Journal: Exp Hematol; 1994 Apr; 22(4):341-7. PubMed ID: 8150032.
    Abstract:
    In this study, we describe the effect of actinomycin D (Act D), 120 micrograms/kg every 2 days, on hematopoiesis over a 48-day period. Erythropoiesis is almost totally eradicated by day 6. Despite continued Act D treatment, however, the block in differentiation between the early (burst-forming units-erythroid [BFU-E]) and late (colony-forming units-erythroid [CFU-E]) erythropoietic progenitor populations is overcome, giving rise to a synchronized and periodic erythrocytosis in both bone marrow and spleen. The first peak is seen on day 27, followed by a second peak on day 41. Circulating erythropoietin (Epo) levels increase from days 16 to 34, indicating that Act D does not have an effect on Epo production. Increasing endogenous Epo levels by bleeding results in an earlier erythroblast and 59Fe incorporation peak than in unbled animals. The BFU-E population increased in number until the block between BFU-E and CFU-E was overcome. No apparent change occurred in either the day 8 colony-forming units-spleen (CFU-S day 8) or granulocyte-macrophage colony-forming cells (GM-CFC) in the bone marrow, although a dramatic increase in GM-CFC in the spleen was observed. It appears that release from the Act D-induced block in differentiation may, in part, be due to Epo, but the mechanism by which this phenomenon takes place is unclear.
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