Further investigations about actinomycin D action on mouse erythropoietin responsive cell.

Repeated injections of 100 micrograms/kg/day of Actinomycin D entirely eradicated erythropoiesis in normal mice. The study of the effect of graded Actinomycin D doses on the erythropoiesis displayed a reproducible dose-effect relationship. The same relation appeared in the action of various Actinomycin D doses on the response to erythropoietin in hypertransfused-mice. To decide whether Actinomycin D had destructive or inhibitory action on its target cell, myleran was used. A single injection of myleran reduced the pluripotent haematopoietic stem cell (CFU) and the erythropoietin responsive cell (ERC) in polycythemic mice to around 1% that of the controls. When repeated injections of erythropoietin restored a transitory ERC population in the absence of CFU, Actinomycin D to the doses of 90 and 120 micrograms/kg-mouse/day did not prevent the erythropoietin effect on self replication of ERC. This result directly showed that Actinomycin D acted on the ERC by selective inhibition of their differentiation without cytotoxic effect.