Reduced permeability in CHO cells as a mechanism of resistance to colchicine

Colchicine resistant (CHr) lines of stable phenotype were isolated from cultured Chinese hamster (CHO) cells. Successive single step selections for increasing resistance were performed by isolating resistant colonies at each step. Two complementary assays involving [³H] colchicine uptake by whole cells and binding of [³H] colchicine by cytoplasmic extracts were developed to test for altered permeability and altered intracellular target protein, respectively. All clones isolated appeared to have decreased permeability to the drug while their colchicine binding ability was not reduced. The amount of reduction in colchicine uptake correlated strongly with cellular resistance. The CHr lines were also cross resistant to other drugs such as actinomycin D, vinblastine and colcemid; furthermore, the degree of cross resistance was positively correlated with the degree of colchicine resistance. The non ionic detergent Tween 80 potentiated the cytotoxic action of colchicine on mutant cells as well as its rate of uptake into whole cells.