Tumor promoters inhibit spontaneous differentiation of Friend erythroleukemia cells in culture.

Clones of Friend erythroleukemia cells, characterized by the presence of 40-70% benzidine-positive cells synthesizing hemoglobin in the absence of inducing drugs, were treated with several phorbol diesters with a known range of tumor-promoting activity on mouse skin. Good correlation was found between the reported tumor-promoting activity of a particular phorbol diester and its ability to inhibit spontaneous erythroid differentiation in culture. The inhibition of differentiation by 12-O-tetradecanoyl-phorbol-13-acetate, the most active tumor promoter, was maximum after 4 days of treatment; this inhibition was reversed by removal of the phorbol diester no matter how long the period of treatment. Unlike control cells, which gradually revert to a population with a low percentage of benzidine-positive cells, cells treated with 12-O-tetradecanoyl-phorbol-13-acetate retained a high potential for spontaneous differentiation.