Colchicine resistant friend cells: Application to the study of actinomycin D induced erythroid differentiation

✍ Scribed by Valerie Crichley; Dixie Mager; Alan Bernstein

• Publisher: John Wiley and Sons
• Year: 1980
• Tongue: English
• Weight: 620 KB
• Volume: 102
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041020110

✦ Synopsis

Abstract

Colchicine resistant (Cch^R^) mutants have been isolated from Friend erythroeleukemic cells by successive single‐step selections. Measurements of the rate of uptake of [^3^H]‐colchicine into whole cells, and the binding of [^3^H]‐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 Cch^R^ 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 Cch^R^ 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 Cch^R^ cells, but had no significant effect on either actinomycin D induction of Cch^S^ cells or DMSO induction of both Cch^S^ and Cch^R^ 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.