title: γ-H2AX as a marker for dose deposition in the brain of wistar rats after synchrotron microbeam radiation.
abstract: OBJECTIVE
  Synchrotron radiation has shown high therapeutic potential in small animal models of malignant brain tumours. However, more studies are needed to understand the radiobiological effects caused by the delivery of high doses of spatially fractionated x-rays in tissue. The purpose of this study was to explore the use of the γ-H2AX antibody as a marker for dose deposition in the brain of rats after synchrotron microbeam radiation therapy (MRT).
  
  
  METHODS
  Normal and tumour-bearing Wistar rats were exposed to 35, 70 or 350 Gy of MRT to their right cerebral hemisphere. The brains were extracted either at 4 or 8 hours after irradiation and immediately placed in formalin. Sections of paraffin-embedded tissue were incubated with anti γ-H2AX primary antibody.
  
  
  RESULTS
  While the presence of the C6 glioma does not seem to modulate the formation of γ-H2AX in normal tissue, the irradiation dose and the recovery versus time are the most important factors affecting the development of γ-H2AX foci. Our results also suggest that doses of 350 Gy can trigger the release of bystander signals that significantly amplify the DNA damage caused by radiation and that the γ-H2AX biomarker does not only represent DNA damage produced by radiation, but also damage caused by bystander effects.
  
  
  CONCLUSIONS
  In conclusion, we suggest that the γ-H2AX foci should be used as biomarker for targeted and non-targeted DNA damage after synchrotron radiation rather than a tool to measure the actual physical doses.
authors: Stereotactic Neurosurgery and Laboratory for Molecular Neurosurgery, Freiburg University Medical Center, Freiburg, Germany; Medical Physics and Applied Radiation Sciences Department, McMaster University, Hamilton, Ontario, Canada.
authors: Cristian
authors: C
authors: Fernandez-Palomo
authors: Medical Physics and Applied Radiation Sciences Department, McMaster University, Hamilton, Ontario, Canada.
authors: Carmel
authors: C
authors: Mothersill
authors: European Synchrotron Radiation Facility, Grenoble, France.
authors: Elke
authors: E
authors: Bräuer-Krisch
authors: Institute of Pathology, University of Bern, Bern, Switzerland.
authors: Jean
authors: J
authors: Laissue
authors: Medical Physics and Applied Radiation Sciences Department, McMaster University, Hamilton, Ontario, Canada.
authors: Colin
authors: C
authors: Seymour
authors: Stereotactic Neurosurgery and Laboratory for Molecular Neurosurgery, Freiburg University Medical Center, Freiburg, Germany; Department of Radiotherapy/Laboratory of Radiobiology, Rostock University Medical Center, Rostock, Germany.
authors: Elisabeth
authors: E
authors: Schültke
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis*; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy; D024201:Bystander Effect / Q000528:radiation effects*; D004249:DNA Damage / Q000528:radiation effects*; D005910:Glioma / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy; D006657:Histones / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D007124:Immunoenzyme Techniques; D008297:Male; D010750:Phosphoproteins / Q000378:metabolism*; D011879:Radiotherapy Dosage; D051381:Rats; D017208:Rats, Wistar; D017356:Synchrotrons; D014407:Tumor Cells, Cultured; D014965:X-Rays / Q000009:adverse effects*
chemical_list: D015415:Biomarkers; D006657:Histones; D010750:Phosphoproteins; C577575:gamma-H2AX protein, rat