Colchicine resistant Friend cells: application to the study of actinomycin D induced erythroid differentiation.

Abstract

AbstractColchicine resistant (CchR) mutants have been isolated from Friend erythroeleukemic cells by successive single‐step selections. Measurements of the rate of uptake of [3H]‐colchicine into whole cells, and the binding of [3H]‐colchicine to cytoplasmic extracts, suggest that these mutants are colchicine‐resistant due to a reduced membrane permeability to colchicine, rather than an altered intracellular colchicine‐binding target. Consistent with this conclusion is the observation that non‐toxic concentrations of Tween–80, a non‐ionic detergent, potentiated colchicine uptake into mutant cells. In addition, these Friend cell mutants, like CchR mutants of other cell types, are cross‐resistant to a variety of unrelated drugs, including daunomycin, puromycin, emetine, and actinomycin D.A comparison of the dose‐response curves for the induction of Friend cell differentiation by actinomycin D of both wild‐type and two CchR cells suggests that actinomycin D permeation is required for its effects on Friend cell differentiation. Potentiation of actinomycin D uptake by Tween–80 significantly lowered the concentration of drug required to induce hemoglobin synthesis in the CchR cells, but had no significant effect on either actinomycin D induction of CchS cells or DMSO induction of both CchS and CchR cells. In common with other chemical inducers of Friend cell differentiation, the addition of actinomycin D results in an early decrease in 86 RbCl uptake, although this effect on transport occurred 14 hours later than that observed with DMSO.