Inhibition of proliferation and differentiation of mouse erythroleukemia cells by hydroxamic acids

The effect of several hydroxamic acids on cell growth and differentiation was studied in vitro in cultures of Friend erythroleukemia cells, line F4-6. Terminal differentiation in F4-6 cells can be induced by exposure to a variety of structurally unrelated compounds or to conditions which inhibit cell growth. Hydroxamic acids do not induce erythroid differentiation but interfere with both cell growth of F4-6 cells and the induction of differentiation by DMSO in these cells. DMSO-induced terminal differentiation is inhibited even when F4-6 cells are pretreated for 24 h with hydroxamates followed by removal of the hydroxamates and transfer to fresh medium containing 1% DMSO. Reduction of cell growth by hydroxamates is completely and immediately reversible upon removal. In contrast, the inhibition of DMSO inducibility is not reversible within 24 h. Cell pretreated with hydroxamates for 24 h prior to a 96 h-exposure to DMSO show the same reduction in synthesis of hemoglobin as cells simultaneously exposed to DMSO and hydroxamates.