Nanosecond Electric Pulses Induce DNA Breaks In Cisplatin-sensitive And–resistant Human Ovarian Cancer Cells

Purpose: The aim of this study was to investigate nsEP-induced DNAdamages and cell-death in cisplatin-sensitive and-resistant human ovariancancer cells in vitro.Method: Human ovarian cancer cells COC1and COC1/DDP (acisplatin-resistant subline) were exposed to6kV/cm nanosecond electricpulses (nsEP) with a pulse length of8,16or24ns. The potential in asubcellular unit was calculated using a multilayer dielectric spherical model,and area under the voltage–time curves (AUC) integrated with a lower limitof0.2V. Cell viability was determined, and double-stand and total DNAbreaks detected with the neutral and alkaline comet assays.Result: nsEP evoked a higher voltage and AUC in nucleoplasm, andthe levels in COC1cells was just above those in COC1/DDP cells. Cometsonly appeared in the alkaline assay demonstrating single-stand DNA break.Fewer DNA break (16.51%vs.35.13%at24ns, p=0.0150) and more survival(22.42%vs.13.19%at24ns, p=0.0015) occurred in COC1/DDP cells despitean equal electric energy and almost equal cell sizes.24-ns EP led to higher rates of cell-death and comet. The comet rate correlated with cell-deathfraction in either cell line (r=0.5701, p=0.0135; r=0.5110, p=0.0302). Therewas no a correlation between the tail length, tail moment or Olive tailmoment and cell-death rate (p=0.8643-0.9478；p=0.5379-0.8630).Conclusion: The data showed that response of chemosensitive cells tonsEP differed from that of chemoresistant cells, and DNA damage led topercent of cell death.