title: Differential Radiosensitivity of Uveal Melanoma Cell Lines After X-rays or Carbon Ions Radiation.
abstract: OBJECTIVE
  We compared the radiosensitivity of uveal melanoma (UM) cell lines after x-ray or carbon-ions radiation (C-ions).
  
  
  METHODS
  We characterized the radiosensitivity toward x-rays and C-ions of UM cell lines: 92.1, MEL270, SP6.5, MKT-BR, μ2, and TP17. Normal choroidal melanocytes and the retinal pigment epithelial cell line ARPE19 were used as controls for normal cells. X-rays were delivered with an energy of 6 MV at a dose rate of 2 Gy/min. X-rays served as a reference for Relative Biological Effectiveness (RBE) evaluation. Radiation with C-ions was delivered at 75 MeV/u (34 keV/μm) at a dose rate of 2 Gy/min. After single-doses (0-8 Gy) of medical x-rays (6 MV) or C-ions (33 keV/μm), cells sensitivity was measured using standard colony formation assay, and cell growth was examined by counting the cell colonies. The effect of x-rays or C-ions on the expression and activation of ERK1/2 was evaluated by Western Blot.
  
  
  RESULTS
  C-ions presented with regard to the x-rays a RBE of 1.9 to 2.5 at 10% of UM cells survival. The x-ray sensitivity of UM cells was neither influenced by the synchronization of cells in phase G0/G1 of the cell cycle nor by the level of oxygenation. X-ray and C-ions radiation had the same effects on cell cycle leading to a mitotic catastrophe that appeared earlier after C-ions than x-ray treatment. However, C-ions radiation induced a sustained inhibition of ERK1/2 activation compared to the transitory induction of that signalization pathway after x-ray radiation.
  
  
  CONCLUSIONS
  This in vitro study shows that C-ions had a better biological effectiveness than x-rays leading to a sustained inhibition of the ERK1/2 pathway.
authors.affiliation: CNRS, UMR6301-ISTCT, CERVOxy group, Caen, France 2Université de Caen Basse-Normandie, CNRS, UMR6301-ISTCT, CERVOxy group, Caen, France 3CEA, CNRS, UMR6301-ISTCT, CERVOxy group, Caen, France.
authors.forename: Armelle
authors.initials: A
authors.lastname: Calipel
authors.affiliation: CNRS, UMR6301-ISTCT, CERVOxy group, Caen, France 2Université de Caen Basse-Normandie, CNRS, UMR6301-ISTCT, CERVOxy group, Caen, France 3CEA, CNRS, UMR6301-ISTCT, CERVOxy group, Caen, France 4CHU de Caen, Service d'Ophtalmologie, Caen, France.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Lux
authors.affiliation: Centre Universitaire d'Ophtalmologie-Recherche, Axe Médecine Régénératrice, Centre de Recherche FRQS du CHU de Québec, Québec, Canada 6Département d'Ophtalmologie, Faculté de Médecine, Université Laval, Québec, Québec, Canada.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Guérin
authors.affiliation: CEA-DSV-IRCM - LARIA, GANIL, Caen, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Lefaix
authors.affiliation: SAPHYN/ARCHADE, Caen, France.
authors.forename: Carine
authors.initials: C
authors.lastname: Laurent
authors.affiliation: CNRS, UMR6301-ISTCT, CERVOxy group, Caen, France 2Université de Caen Basse-Normandie, CNRS, UMR6301-ISTCT, CERVOxy group, Caen, France 3CEA, CNRS, UMR6301-ISTCT, CERVOxy group, Caen, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Bernaudin
authors.affiliation: CNRS, UMR6301-ISTCT, CERVOxy group, Caen, France 3CEA, CNRS, UMR6301-ISTCT, CERVOxy group, Caen, France 5Centre Universitaire d'Ophtalmologie-Recherche, Axe Médecine Régénératrice, Centre de Recherche FRQS du CHU de Québec, Québec, Canada 6Département d'O.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Mouriaux
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D002829:Choroid / Q000166:cytology; D003114:Colony-Forming Units Assay; D004307:Dose-Response Relationship, Radiation; D063193:Heavy Ion Radiotherapy; D006801:Humans; D008544:Melanocytes / Q000528:radiation effects; D008545:Melanoma / Q000201:enzymology / Q000532:radiotherapy*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D011836:Radiation Tolerance; D012062:Relative Biological Effectiveness; D055213:Retinal Pigment Epithelium / Q000528:radiation effects; D014410:Tumor Stem Cell Assay; D014604:Uveal Neoplasms / Q000201:enzymology / Q000532:radiotherapy*; D014965:X-Rays; D000098943:Uveal Melanoma
chemical_list: C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3