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

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...

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Published in:Biochimica et biophysica acta Vol. 1800; no. 11; pp. 1210 - 1219
Main Authors: Ibey, Bennett L., Pakhomov, Andrei G., Gregory, Betsy W., Khorokhorina, Vera A., Roth, Caleb C., Rassokhin, Mikhail A., Bernhard, Joshua A., Wilmink, Gerald J., Pakhomova, Olga N.
Format: Journal Article
Language:English
Published: Netherlands 01.11.2010
Subjects:
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
ISSN:0304-4165, 0006-3002
Online Access:Get full text
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Summary: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. Effects in Jurkat and U937 cells were characterized by survival assays, DNA electrophoresis and flow cytometry. 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. 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. Nanosecond EP can selectively target certain cells in medical applications like tumor ablation.
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ISSN:0304-4165
0006-3002
DOI:10.1016/j.bbagen.2010.07.008