Inhibition of RNA and protein syntheses makes non-differentiating mouse myeloid leukemia cells sensitive to a factor(s) stimulating differentiation

Abstract

Treatment with ascitic fluid from animals bearing various tumors, can induce mouse myeloid leukemia line cells, M1, to differentiate in vitro into macrophages and granulocytes. Cells were isolated that were resistant to the ascitic fluid factor(s) stimulating differentiation (D‐factor). The resistant cells became sensitive to the D‐factor and differentiated after treatment with various inhibitors of RNA synthesis (actinomycin D, nogalamycin, chromomycin A₃ or cordycepin) or protein synthesis (puromycin or cycloheximide). The cells could not be induced to differentiate by treatment with the inhibitors alone. The effective doses of the inhibitors of protein synthesis were toxic to the cells. Among these inhibitors actinomycin D (5 ng/ml) was the most effective for sensitizing the resistant cells. Inhibitors of DNA synthesis did not sensitize the resistant cells. Added actinomycin D was mainly recovered in the nuclear fraction of the cells. The sensitizing effect of actinomycin D on the cells was roughly parallel to the extent of its inhibition of RNA synthesis in the cells. The effective concentration of actinomycin D (5 ng/ml) mainly inhibited the α‐amanitin‐sensitive RNA synthesis, although it also inhibited α‐amanitin‐resistant RNA synthesis to some extent. These results suggest that α‐amanitin‐sensitive RNA synthesis may be involved in sensitization of the resistant cells to the D‐factor.