title: Low-temperature plasma treatment induces DNA damage leading to necrotic cell death in primary prostate epithelial cells.
abstract: BACKGROUND
  In recent years, the rapidly advancing field of low-temperature atmospheric pressure plasmas has shown considerable promise for future translational biomedical applications, including cancer therapy, through the generation of reactive oxygen and nitrogen species.
  
  
  METHODS
  The cytopathic effect of low-temperature plasma was first verified in two commonly used prostate cell lines: BPH-1 and PC-3 cells. The study was then extended to analyse the effects in paired normal and tumour (Gleason grade 7) prostate epithelial cells cultured directly from patient tissue. Hydrogen peroxide (H2O2) and staurosporine were used as controls throughout.
  
  
  RESULTS
  Low-temperature plasma (LTP) exposure resulted in high levels of DNA damage, a reduction in cell viability, and colony-forming ability. H2O2 formed in the culture medium was a likely facilitator of these effects. Necrosis and autophagy were recorded in primary cells, whereas cell lines exhibited apoptosis and necrosis.
  
  
  CONCLUSIONS
  This study demonstrates that LTP treatment causes cytotoxic insult in primary prostate cells, leading to rapid necrotic cell death. It also highlights the need to study primary cultures in order to gain more realistic insight into patient response.
authors.affiliation: York Plasma Institute, Department of Physics, University of York, Heslington, York YO10 5DD, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: Hirst
authors.affiliation: 1] Department of Urology, Castle Hill Hospital, Cottingham, East Yorkshire HU16, 5JQ, UK [2] Hull York Medical School, University of Hull, Hull, East Yorkshire HU6 7RX, UK.
authors.forename: M S
authors.initials: MS
authors.lastname: Simms
authors.affiliation: 1] Department of Urology, Castle Hill Hospital, Cottingham, East Yorkshire HU16, 5JQ, UK [2] Hull York Medical School, University of Hull, Hull, East Yorkshire HU6 7RX, UK.
authors.forename: V M
authors.initials: VM
authors.lastname: Mann
authors.affiliation: YCR Cancer Research Unit, Department of Biology, University of York, Heslington, York YO10 5DD, UK.
authors.forename: N J
authors.initials: NJ
authors.lastname: Maitland
authors.affiliation: York Plasma Institute, Department of Physics, University of York, Heslington, York YO10 5DD, UK.
authors.forename: D
authors.initials: D
authors.lastname: O'Connell
authors.affiliation: YCR Cancer Research Unit, Department of Biology, University of York, Heslington, York YO10 5DD, UK.
authors.forename: F M
authors.initials: FM
authors.lastname: Frame
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D002478:Cells, Cultured; D003080:Cold Temperature; D004249:DNA Damage / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D009336:Necrosis; D058626:Plasma Gases / Q000494:pharmacology*; D011467:Prostate / Q000187:drug effects / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology*
chemical_list: D058626:Plasma Gases; D006861:Hydrogen Peroxide
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