Tumor-promoting phorbol esters stimulate myelopoiesis and suppress erythropoiesis in cultures of mouse bone marrow cells.

Tumor-promoting phorbol esters affect the ability of mouse hematopoietic progenitor cells to form morphologically recognizable colonies in culture. They induce myeloid progenitor cells to form colonies of the monocyte/macrophage type in the absence of exogenous granulocyte/macrophage colony-stimulating factor. Conversely, similar concentrations of tumor-promoting phorbol esters inhibit the formation of colonies (bursts) by early erythroid progenitor cells, even when the culture medium contains saturating amounts of burst-promoting activity and erythropoietin. However, late erythroid progenitor cells, are not affected by phorbol esters. Only a temporary (45 min) exposure of marrow cells to phorbol esters is necessary to produce both stimulation of myeloid colony growth and inhibition of erythroid burst formation. Experiments with a radioactively labeled phorbol ester indicate a high affinity for cellular binding sites. The ability of various phorbol esters to stimulate myeloid colony growth and to inhibit erythroid burst formation correlates well with their ability to promote skin tumors in mice. The different responses of two developmentally closely related hematopoietic progenitor cells to the same phorbol esters indicate the usefulness of these substances in the further analysis of regulatory events affecting hematopoiesis.