title: Evaluation of low-dose proton beam radiation efficiency in MIA PaCa-2 pancreatic cancer cell line vitality and H2AX formation.
abstract: OBJECTIVE
  The aim of this study was to evaluate the efficiency of proton beam irradiation in pancreatic cancer cell line MIA PaCa-2 and its role in the cell cycle, apoptosis, and formation of histone γH2AX in different reparation times (72-h follow-up).
  
  
  METHODS
  The MIA PaCa-2 pancreatic carcinoma cell line was irradiated with 1.6-Gy proton beam. After irradiation, cell viability was measured colorimetrically, and the cell cycle, apoptosis, and γH2AX expression were evaluated on a FACScan cytometer.
  
  
  RESULTS
  Low-dose proton beam irradiation had an effect on the MIA PaCa-2 tumor cell line already 1h after exposure, but maximal lethality was reached after 72h postirradiation with a cell viability rate of 24%. The cell cycle went into partial G1/0 arrest, and was released after 72h. The expression of γH2AX was strong and its levels were significantly elevated as late as 48h post radiation. The apoptosis levels increased with post radiation incubation time to reach 79% after 72h.
  
  
  CONCLUSIONS
  Our data demonstrate that low-doses proton beam irradiation had an effect on MIA PaCa-2 pancreatic carcinoma cell line. Full extent of irradiation had an impact only 24h postirradiation, triggering DNA arrested cell cycle in G1/0 phase. Formed DNA DSBs were found to be repaired via the NHEJ pathway mechanism within 72h. Unsuccessful repaired DSBs induced apoptotic cell death. After 72h reparation processes were completed, and cell cycle was released from arrest in G1/0 phase.
authors.affiliation: Department of Stem Cell Biology, State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania. Electronic address: liubaviciute@gmail.com.
authors.forename: Aušra
authors.initials: A
authors.lastname: Liubavičiūtė
authors.affiliation: Laboratory of Immunology, National Cancer Institute, Vilnius, Lithuania.
authors.forename: Jan Aleksander
authors.initials: JA
authors.lastname: Kraśko
authors.affiliation: Laboratory of Immunology, National Cancer Institute, Vilnius, Lithuania.
authors.forename: Agata
authors.initials: A
authors.lastname: Mlynska
authors.affiliation: Laboratory of Immunology, National Cancer Institute, Vilnius, Lithuania; Department of Nuclear Research, Institute of Physics, Center for Physical Sciences and Technology, Vilnius, Lithuania.
authors.forename: Jelena
authors.initials: J
authors.lastname: Lagzdina
authors.affiliation: Laboratory of Molecular Oncology, National Cancer Institute, Vilnius, Lithuania.
authors.forename: Kęstutis
authors.initials: K
authors.lastname: Sužiedėlis
authors.affiliation: Laboratory of Immunology, National Cancer Institute, Vilnius, Lithuania.
authors.forename: Vita
authors.initials: V
authors.lastname: Pašukonienė
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D002453:Cell Cycle / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D006657:Histones / Q000378:metabolism*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D061766:Proton Therapy / Q000379:methods*
chemical_list: D006657:Histones
keywords: Double strand breaks; Gamma H2AX; MIA PaCa-2; Non-homologous end joining; Proton irradiation