Gain and loss of hypersensitivity to resistance modifiers in multidrug resistant Chinese hamster ovary cells.

Some, but not all, multidrug resistant cell lines exhibit collateral hypersensitivity to resistance modifiers. We have examined the relationship between levels of P-glycoprotein expression and resistance modifier hypersensitivity in Chinese hamster ovary cell lines. We have defined a model system for the gain and loss of such sensitivity which indicates that its presence is not simply proportional to P-glycoprotein levels, but is acquired only above a certain level of P-glycoprotein expression. We also show that previously reported differences in such sensitivity between lines is not attributable to differences in genetic background of the cell lines used for selection of drug resistance.