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

Biochim Biophys Acta. 2010 Nov;1800(11):1210-9. doi: 10.1016/j.bbagen.2010.07.008. Epub 2010 Aug 3.

Abstract

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.

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 (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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Apoptosis / radiation effects*
  • Cell Membrane / metabolism
  • Cell Membrane / pathology*
  • Cell Membrane / radiation effects*
  • Cell Membrane Permeability / radiation effects*
  • DNA Damage
  • Electromagnetic Fields*
  • Electroporation
  • Flow Cytometry
  • Humans
  • Jurkat Cells
  • Organelles / metabolism
  • Organelles / pathology
  • Organelles / radiation effects
  • Phosphatidylserines / metabolism
  • U937 Cells

Substances

  • Phosphatidylserines