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 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.


CONCLUSIONS
Nanosecond EP can selectively target certain cells in medical applications like tumor ablation.
Ibey
Bennett L
BL
Radio Frequency Radiation Branch, 711th Human Performance Wing, Air Force Research Laboratory, Brooks City-Base, San Antonio, TX, USA.
Pakhomov
Andrei G
AG
Gregory
Betsy W
BW
Khorokhorina
Vera A
VA
Roth
Caleb C
CC
Rassokhin
Mikhail A
MA
Bernhard
Joshua A
JA
Wilmink
Gerald J
GJ
Pakhomova
Olga N
ON
D017209:Apoptosis / Q000528:radiation effects*; D002462:Cell Membrane / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects*; D002463:Cell Membrane Permeability / Q000528:radiation effects*; D004249:DNA Damage; D004574:Electromagnetic Fields; D018274:Electroporation; D005434:Flow Cytometry; D006801:Humans; D019169:Jurkat Cells; D015388:Organelles / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D010718:Phosphatidylserines / Q000378:metabolism; D020298:U937 Cells
D010718:Phosphatidylserines