title: Response of a radioresistant human melanoma cell line along the proton spread-out Bragg peak.
abstract: OBJECTIVE
  To analyse changes of cell inactivation and proliferation under therapeutic irradiation conditions along the proton spread out Bragg peak (SOBP) with particular emphasis on its distal declining edge.
  
  
  METHODS
  HTB140 cells were irradiated at four positions: plateau, middle, distal end and distal declining edge of the 62 MeV proton SOBP. Doses ranged from 2-16 Gy. They were normalised in the middle of SOBP and delivered following the axial physical dose profile. Survival, proliferation and cell cycle were assessed seven days after irradiation.
  
  
  RESULTS
  Moving from proximal to distal irradiation position surviving fractions at 2 Gy (SF2) decreased from 0.88-0.59. Increased radiosensitivity of the cells was noticed for the doses below 4 Gy, resulting in two gradients of cell inactivation, stronger for lower and weaker for higher doses. Relative biological effectiveness (RBE) increased from 1.68-2.84 at the distal end of SOBP. A further rise of RBE reaching 7.14 was at its distal declining edge. Following the axial physical dose profile of SOBP the strongest inactivation was attained at its distal end and was comparable to that at its declining edge.
  
  
  CONCLUSIONS
  Survival data confirmed very high radioresistance of HTB140 cells. An effect similar to low-dose hyper radiosensitivity (HRS) was observed for order of magnitude larger doses. Better response of cells to protons than to gamma-rays was illustrated by rather high RBE. Strong killing ability at the SOBP distal declining edge was the consequence of increasing proton linear energy transfer.
authors.affiliation: Vinca Institute of Nuclear Sciences, Belgrade, Serbia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Petrović
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Ristić-Fira
authors.forename: Danijela
authors.initials: D
authors.lastname: Todorović
authors.forename: Lela
authors.initials: L
authors.lastname: Korićanac
authors.forename: Lucia
authors.initials: L
authors.lastname: Valastro
authors.forename: Pablo
authors.initials: P
authors.lastname: Cirrone
authors.forename: Giacomo
authors.initials: G
authors.lastname: Cuttone
mesh_terms: D002453:Cell Cycle / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D018499:Linear Energy Transfer; D008545:Melanoma / Q000473:pathology / Q000532:radiotherapy*; D061766:Proton Therapy; D011836:Radiation Tolerance; D012062:Relative Biological Effectiveness; D011522:Protons
chemical_list: D011522:Protons