4.6 Article

Nanosecond electric pulses induce DNA breaks in cisplatin-sensitive and -resistant human ovarian cancer cells

Journal

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2012.11.089

Keywords

Nanosecond electric pulse; Chemoresistance; Ovarian cancer; DNA break; Cell death

Funding

  1. Natural Science Foundation of China [11174376]
  2. Natural Science Foundation of Chongqing [CSTC 2009BA5049]

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Human ovarian cancer cells COC1 and COC1/DDP (cisplatin-resistant subline) were exposed to 6 kV/cm nanosecond electric pulses (nsEP) with a pulse length of 8, 16 or 24 ns. The potential in a subcellular unit was calculated using a multilayer dielectric spherical model, and area under the voltage-time curves (AUC) integrated with a lower limit of 0.2 V. Cell viability was determined, and double-stand and total DNA breaks detected with the neutral and alkaline comet assays. nsEP evoked a higher voltage and AUC in nucleoplasm, and the levels in COD cells was just above those in COC1/DDP cells. Comets only appeared in the alkaline assay demonstrating single-stand DNA break. Fewer DNA break (16.51% vs. 35.13% at 24 ns, p = 0.0150) and more survival (22.42% vs. 13.19% at 24 ns, p = 0.0015) occurred in COC1/DDP cells despite an 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-death fraction in either cell line (r = 0.5701, p = 0.0135; r = 0.5110, p = 0.0302). There was no a correlation between the tail length, tail moment or Olive tail moment and cell-death rate. The data showed that response of chemosensitive cells differed from that of chemoresistant cells and DNA damage contributed to percent of cell death. (C) 2012 Elsevier Inc. All rights reserved.

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