ASSOCIATION OF BCL-2 WITH MEMBRANE HYPERPOLARIZATION AND RADIORESISTANCE

The resting membrane potential of parental, neomycin control, and Bcl- 2 transfected cells was measured, and the effect of membrane hyperpola rization or depolarization on radiosensitivity was studied. Bcl-2 tran sfected cells were significantly more radioresistant than control cell s and were significantly hyperpolarized compared to parental and neomy cin control transfected PW and HL60 cells. Hyperpolarization of the pa rental and neomycin control transfected cells by valinomycin significa ntly increased the radioresistance of these cells to such an extent th at there was no longer a significant difference in the survival of the valinomycin treated and irradiated control cells compared to similarl y irradiated Bcl-2 transfected cells. In contrast, depolarization of t he Bcl-2 transfected PW and HL60 cells decreased the radioresistance o f the Bcl-2 transfectants to a level similar to that of the control ce lls. The data presented here suggest that overexpression of Bcl-2 affe cts membrane potential and that this hyperpolarization is associated w ith increased radioresistance of cells that overexpress Bcl-2. Further more, Bcl-2 transfected cells were also less susceptible to the specif ic Na+/K+-ATPase inhibitor ouabain, suggesting that Bcl-2 may act at t he level of the Na+/K+-ATPase pump. (C) 1996 Wiley-Liss, Inc.