POLAR APOLAR COMPOUNDS INDUCE LEUKEMIA-CELL DIFFERENTIATION BY MODULATING CELL-SURFACE POTENTIAL

The mechanism of action of polar/apolar inducers of cell differentiati on, such as dimethyl sulfoxide and hexamethylene-bisacetamide, is stil l obscure. In this paper evidence is provided that their effects on mu rine erythroleukemia cells are modulated by various extracellular cati ons as a precise function of the cation effects on membrane surface po tential. The interfacial effects of the inducers were directly measure d on the charged electrode, showing that both dimethyl sulfoxide and h examethylene-bisacetamide, at the effective concentrations for cell di fferentiation and within the physiological range of charge density, ad sorb at the charged surface and produce a potential shift. A linear co rrelation was found between this shift and the inducer effects on cell differentiation. Besides offering a different interpretation of the m echanism of action of the inducers, these findings indicate that surfa ce potential has a signaling function. They may also be relevant to ca ncer treatments based on tumor-cell commitment to terminal differentia tion.