Characterization of multidrug resistance in SEWA mouse tumor cells: increased glutathione transferase activity and reversal of resistance with verapamil.

: The glutathione transferase (EC 2.5.1.18) activity of multidrug-resistant and drug-sensitive SEWA mouse tumor cells was determined. Increase in activity was found in all multidrug-resistant sublines. Electrophoretic separation of cytosolic proteins and immunodetection, using antisera against Class Alpha, Class Mu and Class Pi glutathione transferase, revealed a two-fold increase of the Class Pi transferase in the resistant cells. The role of glutathione transferase of Class Pi in the multidrug resistance and its distinction from the over-produced 21,000 dalton protein p21 is discussed. Reversal of the resistance, using the calcium antagonist verapamil, and different sensitivity to verapamil between different sublines are also reported.