title: Effects of low energy protons on clonogenic survival, DSB repair and cell cycle in human glioblastoma cells and B14 fibroblasts.
abstract: OBJECTIVE
  The reaction of human tumor cells and mammalian normal tissue to irradiation with low energy protons and X-rays was examined.
  
  
  METHODS
  An irradiation facility with a vertical proton beam was set up at the Tandem accelerator at the University of Erlangen. U-138MG human glioblastoma cells and B14 hamster fibroblasts were irradiated with 5.7 and 7.0 MeV protons (LET 7.27 and 6.23 keV/microm) and with 120 kV X-rays. The inactivation was measured by the colony forming assay, induction and repair of DNA double strand breaks (DSB) by constant field gel electrophoresis and cell cycle control by image cytometry.
  
  
  RESULTS
  An obvious reduction of the shoulder of the dose effect curve was determined. This effect was more pronounced for the glioblastoma cell line. The RBE at 10% survival was measured as 1.78 +/- 0.09 for glioblastoma cells and 1.18 +/- 0.06 for B14 fibroblasts. The induction of DNA DSB in glioblastoma cells showed an RBE of 0.96 +/- 0.06, after 24h repair time an RBE of 2.63 +/- 0.07 was calculated. Protons had a larger and enduring effect on G2 arrest of cell cycle than X-rays, 72 hours after irradiation with 10 Gy an RBE of 1.57 +/- 0.05 was calculated.
  
  
  CONCLUSIONS
  The effect of higher LET irradiation was more distinct for tumor cells than for normal tissue. Both cell lines showed a higher RBE for cell survival than the value of 1.1 normally used for proton therapy. Repair capacity of DNA DSB was reduced following low energy proton irradiation and G2 arrest was induced to a larger degree. Further experiments are needed to elucidate if this could be a reason for lower cell survival.
authors.affiliation: Department of Radiation Therapy, University Hospital Erlangen, Universitaetsstrasse 27, 91054 Erlangen, Germany. heiner.moertel@strahlen.med.uni-erlangen.de
authors.forename: Heinrich
authors.initials: H
authors.lastname: Moertel
authors.forename: Jens-Christoph
authors.initials: JC
authors.lastname: Georgi
authors.forename: Luitpold
authors.initials: L
authors.lastname: Distel
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Eyrich
authors.forename: Miriam
authors.initials: M
authors.lastname: Fritsch
authors.forename: Gerhard
authors.initials: G
authors.lastname: Grabenbauer
authors.forename: Rolf
authors.initials: R
authors.lastname: Sauer
mesh_terms: D002453:Cell Cycle / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D061766:Proton Therapy; D012062:Relative Biological Effectiveness; D011522:Protons
chemical_list: D011522:Protons