Inhibition of Dimethyl Sulfoxide Induced Erythropoietic Differentiation of Murine Erythroleukemia Cells in Culture1

The dimethyl sulfoxide induced erythropoietic differentiation of murine erythroleukemia cells, as determined by scoring benzidine positive cells, is inhibited by mitomycin C at concentrations that have no effect on cell proliferation. The inhibition occurs only when cells are treated with mitomycin C during induction and has a limit value of about 50%, independent of mitomycin C concentration. This limit value does not depend on cell heterogeneity since genetically homogeneous subclones, derived from DS19 clone, show levels of mitomycin C inhibition between 16 and 50%. Treatment with mitomycin C at different times after dimethyl sulfoxide addition shows that cell sensitivity to inhibition is not homo geneous during the induction period; it is maximal between 18 and 24 h from the start of induction and is observed with a concentration of mitomycin C as low as 25 ÕM. The inhibition of the benzidine positive phenotypic expression appears irreversible since this effect is observed on cells even several generations after those which were actually treated.