Dose-Dependent Thresholds of 10-ns Electric Pulse Induced Plasma Membrane Disruption and Cytotoxicity in Multiple Cell Lines
Abstract
In this study, we determined the LD(50) (50% lethal dose) for cell death, and the ED(50) (50% of cell population staining positive) for propidium (Pr) ion uptake, and phosphatidylserine (PS) externalization for several commonly-studied cell lines (HeLa, Jurkat, U937, CHO-K1, and GH3) exposed to 10-ns electric pulses (EP). We found that the LD(50) varied substantially across the cell lines studied, increasing from 51 J/g for Jurkat cells to 1861 J/g for HeLa cells. PS externalized at doses equal or lower than that required for death in all cell lines ranging from 51 J/g in Jurkat cells to 199 J/g in CHO-K1 cells. Propidium ion uptake occurred at doses lower than required for death in three cell lines: 656 J/g for CHO-K1, 634 J/g for HeLa, and 142 J/g for GH3. Jurkat and U937 cell lines both showed substantial cell death prior to the ED50 for propidium ion uptake at 780 J/g and 1274 J/g, respectively. The mechanism responsible for differences observed amongst the studied cell lines was explored by evaluating cell size, calcium concentration in the exposure medium, and effect of trypsin treatment prior to exposure. None of the studied parameters correlated with the observed results suggesting that cellular susceptibility to injury and death by 10-ns EP may partially depend on cellular physiology. In contrast to previous studies, this evidence suggests that permeabilization of internal membranes may not necessary be responsible for cell death by 10-ns EP. A mixture of Jurkat and HeLa cells was exposed to 10-ns EP at a dose of 280 J/g. Death was observed in the Jurkat cell and not in the HeLa population providing evidence that 10-ns EP may provide a method for selectively killing cells within a heterogeneous tissue.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2010
- Accession Number
- ADA538157
Entities
People
- Andrei G Pakhomov
- Bennett L. Ibey
- Caleb C Roth
- Gerald J. Wilmink
- Joshua A. Bernhard
- Olga N Pakhomova
Organizations
- 711th Human Performance Wing