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Nanosecond pulsed electric field (nsPEF) effects on cells and tissues: apoptosis induction and tumor growth inhibition

Pulse power technology using high intensity (up to 300 kV/cm) nanosecond pulsed electric fields (nsPEF) has been applied for decontamination and amelioration of biofouling, but until now effects on human cells have not been investigated. To analyze structural and functional changes in human cells and solid tumors following exposure to nsPEF we utilized flow cytometry and immunofluorescence microscopy. We provide further support for the hypothesis that as the pulse duration is decreased, there is a lower incidence of electric field interactions at the plasma membrane and a higher incidence of interactions with intracellular structures. The nsPEF effects are pulse duration/electric field intensity-dependent and energy density- or temperature-independent. We also show that nsPEF induces programmed cell death (apoptosis) in cultured cells as indicated by cell shrinkage, Annexin-V-FITC binding to phosphatidylserine on intact cells, and caspase activation. Mouse fibrosarcoma tumors exposed to nsPEF exhibit fragmented DNA and reduced tumor growth in a mouse model. These studies show that nsPEF effects are distinctly different than electroporation pulses and provide the first evidence for the potential application of nsPEF to induce apoptosis and inhibit tumor growth.