Electrical pulse induced changes in cell population dynamics

Summary form only given. Pulsed electric fields (PEFs) are frequently used to permeabilize the cell membrane so that chemotherapeutics, DNA, and other molecules unable to enter the cell can traverse the cell membrane. Our laboratory recently used intense, ultrawideband (UWB) electrical pulses with chemotherapeutics to kill leukemia cells in numbers greater than predicted by simple addition of the killing effects for the individual modalities. Another group observed that applying UWB pulses to neoplastic mammary cells can actually increase cell proliferation. In these and other cancer treatment methods, the stage of the cell cycle targeted is crucial to the treatment´s overall effectiveness because a method that targets proliferating cells has a greater probability of long-term success than one that targets the quiescent (resting) cells. We present results for a population study of Jurkat (human leukemia) cells exposed to multiple 400 mus, 1 kV/cm electrical pulses and various levels of bleomycin, a standard chemotherapeutic. We assess the cell stage targeted by these treatments by fitting the data to a simple mathematical model, which considers the cells as being either proliferating or quiescent. Based on the resulting parameters, we predict how the treatments alter the steady-state behavior and the transition rates between the cell states. We also discuss the possible implications of these results with respect to cancer treatment. The mathematical model used here is general and can also be applied to the population dynamics changes induced by other modalities, such as ultrashort PEFs