Selective cytotoxicity of intense nanosecond-duration electric pulses in mammalian cells |
| |
Authors: | Bennett L Ibey Andrei G Pakhomov Betsy W Gregory Vera A Khorokhorina Caleb C Roth Mikhail A Rassokhin Joshua A Bernhard Gerald J Wilmink Olga N Pakhomova |
| |
Institution: | 1. Radio Frequency Radiation Branch, 711th Human Performance Wing, Air Force Research Laboratory, Brooks City-Base, San Antonio, TX, USA;2. Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA, USA;3. General Dynamics Information Technology, Brooks City-Base, San Antonio, TX, USA |
| |
Abstract: | BackgroundNanosecond 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.MethodsEffects in Jurkat and U937 cells were characterized by survival assays, DNA electrophoresis and flow cytometry.Results10-ns EP caused apoptotic or necrotic death within 2–20 h. Survival (S, %) followed the absorbed dose (D, J/g) as: S = αD(−K), where coefficients K and α determined the slope and the “shoulder” of the survival curve. K was similar in all groups, whereas α 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.Conclusions1.8- 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 significanceNanosecond EP can selectively target certain cells in medical applications like tumor ablation. |
| |
Keywords: | EP electric pulses IRE irreversible electroporation nsEP nanosecond-duration electric pulses PS phosphatidylserine MTT 3-(4 5-Dimethylthiazol-2-yl)-2 5-diphenyltetrazolium bromide |
本文献已被 ScienceDirect 等数据库收录! |
|