Selective cytotoxicity of intense nanosecond-duration electric pulses in mammalian cells

Background: Nanosecond electric pulses (EP) disrupt cell membrane and organelles and cause cell death in a manner different from the conventional irreversible electroporation. We explored the cytotoxic effect of Ions EP (quantitation, mechanisms, efficiency, and specificity) in comparison with 300-ns, 1.8- and 9-mu s EP. Methods: Effects in Jurkat and 0937 cells were characterized by survival assays. DNA electrophoresis and flow cytometry. Results: 10-ns EP caused apoptotic or necrotic death within 2-20 h. Survival (S, %) followed the absorbed dose (D, J/g) as: S=alpha D(-K), where coefficients K and a determined the slope and the "shoulder" of the survival curve. K was similar in all groups, whereas a was cell type- and pulse duration-dependent. Long pulses caused immediate propidium uptake and phosphatidylserine (PS) externalization, whereas 10-ns pulses caused PS externalization only. Conclusions: 1.8- and 9-mu s EP cause cell death efficiently and indiscriminately (LD50 1-3 J/g in both cell lines); 10-ns EP are less efficient, but very selective (LD50 50-80 J/g for Jurkat and 400-500 J/g for U937); 300-ns EP show intermediate effects. Shorter EP open propidium-impermeable, small membrane pores ("nanopores"), triggering different cell death mechanisms. General significance: Nanosecond EP can selectively target certain cells in medical applications like tumor ablation. (C) 2010 Elsevier B.V. All rights reserved.