The autonomous release of erythropoietic inhibition during long-term in vivo administration of actinomycin D.
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.
Rich
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IN
Department of Transfusion Medicine, University of Ulm, Germany.
Kubanek
B
B
D000818:Animals; D001772:Blood Cell Count; D001854:Bone Marrow Cells; D003114:Colony-Forming Units Assay; D003609:Dactinomycin / Q000008:administration & dosage*; D015672:Erythroid Precursor Cells / Q000378:metabolism; D004920:Erythropoiesis / Q000187:drug effects*; D005260:Female; D051379:Mice; D008808:Mice, Inbred CBA; D013154:Spleen / Q000166:cytology; D013997:Time Factors
D003609:Dactinomycin