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Colchicine resistance in human cell lines. Pleiotropic phenotype and decreased membrane permeability
Abstract:
Colchicine-resistant human cells were initially observed in patients exhibiting C-anaphases or tetraploidy in lymphocyte cultures. Cell lines established from these patients displayed cross-resistances to daunomycin, emetine, vinblastine, and vincristine and collateral sensitivity to Xylocaine, showing a pleiotropic phenotype similar to that described in permeability mutants in CHO cells. 3H colchicine uptake and binding assays confirmed a decreased permeability to the drug.
Insights
Colchicine-resistant human cells exhibit cross-resistance to other drugs and reduced drug uptake. This suggests a defect in cell membrane permeability, impacting drug transport and cellular drug levels.
Area of Science:
- Cell Biology
- Pharmacology
- Genetics
Background:
- Colchicine resistance in human cells is a complex phenomenon.
- Previous studies in Chinese Hamster Ovary (CHO) cells identified permeability mutants.
- Understanding resistance mechanisms is crucial for cancer therapy.
Purpose of the Study:
- To investigate the characteristics of colchicine-resistant human cell lines.
- To determine the underlying mechanisms of this resistance.
- To compare the phenotype with known drug-resistant cell models.
Main Methods:
- Establishing cell lines from patients with C-anaphases or tetraploidy.
- Phenotypic analysis of drug resistance and sensitivity.
- Radiolabeled colchicine uptake and binding assays.
Main Results:
- Human cell lines showed cross-resistance to daunomycin, emetine, vinblastine, and vincristine.
- These cells exhibited collateral sensitivity to Xylocaine.
- Decreased 3H colchicine uptake and binding confirmed reduced drug permeability.
Conclusions:
- Colchicine resistance in these human cells is associated with a pleiotropic drug-resistant phenotype.
- Reduced cell membrane permeability is a key mechanism underlying colchicine resistance.
- This finding has implications for understanding multidrug resistance in human cells.