Abstract
Tumor
ablation by nanosecond pulsed electric fields (nsPEF) is an emerging
therapeutic modality. We compared nsPEF cytotoxicity for human cell lines of
cancerous (IMR-32, Hep G2, HT-1080, and HPAF-II) and non-cancerous origin (BJ
and MRC-5) under strictly controlled and identical conditions. Adherent cells were
uniformly treated by 300-ns PEF (0-2000 pulses, 1.8 kV/cm, 50 Hz) on
indium tin oxide-covered glass coverslips, using the same media and serum.
Cell survival plotted against the number of pulses displayed three distinct
regions (initial resistivity, logarithmic survival decline, and residual
resistivity) for all tested cell types, but with differences in LD50 spanning
as much as nearly 80-fold. The non-cancerous cells were less sensitive than
IMR-32 neuroblastoma cells but more vulnerable than the other cancers
tested. The cytotoxic efficiency showed no apparent correlation with cell or
nuclear size, cell morphology, metabolism level, or the extent of membrane
disruption by nsPEF. Increasing pulse duration to 9 µs (0.75 kV/cm,
5 Hz) produced a different selectivity pattern, suggesting that
manipulation of PEF parameters can, at least for certain cancers, overcome
their resistance to nsPEF ablation. Identifying mechanisms and cell markers of
differential nsPEF susceptibility will critically contribute to the proper
choice and outcome of nsPEF ablation therapies.
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