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 10-ns EP (quantitation, mechanisms, efficiency, and specificity) in comparison with 300-ns, 1.8- and 9-μs EP.
Conclusions
1.8- and 9-μs EP cause cell death efficiently and indiscriminately (LD₅&sub0; 1-3 J/g in both cell lines); 10-ns EP are less efficient, but very selective (LD₅&sub0; 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.
Methods
Effects in Jurkat and U937 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=alphaD((-K)), where coefficients K and alpha determined the slope and the "shoulder" of the survival curve. K was similar in all groups, whereas alpha 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-μs EP cause cell death efficiently and indiscriminately (LD₅&sub0; 1-3 J/g in both cell lines); 10-ns EP are less efficient, but very selective (LD₅&sub0; 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.
Significance
Nanosecond EP can selectively target certain cells in medical applications like tumor ablation.