Pleiotropic phenotype of colchicine‐resistant CHO cells: Cross‐resistance and collateral sensitivity

Abstract

Colchicine resistant (CHR) mutants of CHO cells with reduced permeability to colchicine display extensive cross-resistance to a number of apparently unrelated compounds including puromycin, daunomycin, emetine, ethidium bromide and gramicidin D. A positive correlation was observed between the level of cross-resistance and the relative hydrophobicity of these compounds. The mutants also showed increased (collateral) sensitivity to local anaesthetics (procaine, tetracaine, xylocaine and propanolol), steroid hormones (1-dehydrotestosterone, corticosterone and 5beta-pregnan-3,20-dione) and some Triton X compounds. In general, the degree of the pleiotropic response (cross-resistance or collateral sensitivity) correlated with the degree of colchicine resistance in mutant lines. These results are consistent with the pleiotropic phenotype being the result of the same mutation(s) which confer colchicine resistance and support a model for resistance in which the reduced permeability is assumed to be the result of an alteration in the modulation of the fluidity of the surface membrane.

Identification of a novel calcium‐binding protein (CP22) in multidrug‐resistant murine and hamster cells

“…Somatic mammalian cells selected for resistance to one type of cytotoxic drug frequently develop resistance to drugs of unrelated structure and function [1,2]. The mechanisms underlying this multidrug resistance (MDR) phenomenon are unknown, but evidence exists that both decreased drug penetration [3-51 and increased drug efflux occur in resistant cells.…”

Investigation of the relationship between altered intracellular pH and multidrug resistance in mammalian cells

“…In the present manuscript, we have also observed this phenomenon in a number of different multidrug resistant cell lines. Further, to explore the relevance of this change in pH, to the phenomenon of multidrug resistance, the effect of several agents which are known to cause reversal of MDR (verapamil, cyclosporin A) or to inhibit Na+/H+ antiport activity (amiloride) (Bech-Hansen et al, 1976;Biedler & Riehm, 1970;Gupta, 1983Gupta et al, 1988Akiyama et al, 1985). The cells were grown in a-MEM medium supplemented with 7% fetal bovine serum at 37°C in a humidified incubator in an atmosphere of 95% air and 5% CO2.…”

Prediction of the clinical chemotherapeutic response of stage III lung adenocarcinoma patients by an in vitro short term test

“…alkaloids, anthracyclines and antibiotics). This phenomenon has been designated as pleiotropic or multidrug resistance (Bech-Hansen et al, 1976). With this in mind we used in the present prospective study a simple test in which a tumour cell suspension is prepared from the fresh surgical specimen, treated with adriamycin and the uptake of radioactive nucleic acid precursors is determined (Volm et al, 1979;Volm, 1984 daily, repeated every 6 weeks for 4-6 cycles.…”