The Restorative Effect of Erythropoietic Stimulation Upon the Sublethally Irradiated (SLI) Hematopoietic Stem Cell And/or Its Progeny

Bone marrow cells from sublethally irradiated donor mice injected into supralethally (1000 R) irradiated recipients produced not only many fewer spleen colonies but fewer erythrocytic (E) colonies in relation to the number of granulocytic (G) colonies than did unirradiated donor marrow in similar recipients. This reversal of E:G ratio was partially or completely restored by a strong erythropoietic stimulus in the recipients, whether endogenous, (induced by anemia) or exogenous (injected purified EP). Such a stimulus produced a large increase in total spleen colony numbers in all experiments. An unexpected result was a major increase in granulocytic and megakaryocytic colonies in the spleen and marrow of the erythropoietically stimulated recipients. It was concluded that the sublethal irradiation to the donor either produced or revealed a subpopulation of potential colony forming cells whose cell cycle was slow or temporarily arrested. The added EP (and/or related substances) was proposed to have either overridden or induced repair or radiation defect, or stimulated a small and normally undetectable population requiring high levels of stimulant to induce cycling. The result was the expression of their progeny as colonies, whose differentiative type depended upon the kind of hematpoietic inducing microenvironment in which they had lodged.