Taxol resistant mutants of Chinese hamster ovary cells: genetic biochemical, and cross-resistance studies.

摘要: The effects of the microtubule inhibitor taxol on growth and viability Chinese hamster ovary (CHO) cells have been examined. Stable mutants which are between seven to 11-fold more resistant selected in a single step from ethyl methanesulfonate-mutagenized CHO cells. two taxol-resistant (TaxR-1 TaxR-2) studied detail exhibit novel strikingly different cross-resistance/collateral sensitivity patterns various inhibitors. For example, TaxR-1 mutant exhibits increased resistance vinblastine, but comparison parental cells, it shows enhanced toward colchicine, colcemid, stegnacine, griseofulvin. However, this other unrelated compounds, e.g., puromycin, daunomycin, etc., remained largely unaltered. specific pattern cross-resistance/collateral-sensitivity inhibitors suggests that genetic lesion may be affecting microtubule-related component. TaxR-2 mutant, contrast, is highly including maytan-sine, podophyllotoxin. This also greatly cross-resistance ethidium bromide, VM-26 (compounds do not inhibit assembly), reduced cellular uptake 3H-daunomycin indicating nonspecifically affects membrane permeability drugs. cell hybrids formed (or mutant(s)) taxol-sensitive line intermediate levels drug, TaxR phenotypes both these behave codominantly under conditions.