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Title: Involvement of the Artemis Protein in the Relative Biological Efficiency Observed With the 76-MeV Proton Beam Used at the Institut Curie Proton Therapy Center in Orsay

Purpose: Previously we showed that the relative biological efficiency for induced cell killing by the 76-MeV beam used at the Institut Curie Proton Therapy Center in Orsay increased with depth throughout the spread-out Bragg peak (SOBP). To investigate the repair pathways underlying this increase, we used an isogenic human cell model in which individual DNA repair proteins have been depleted, and techniques dedicated to precise measurements of radiation-induced DNA single-strand breaks (SSBs) and double-strand breaks (DSBs). Methods and Materials: The 3-Gy surviving fractions of HeLa cells individually depleted of Ogg1, XRCC1, and PARP1 (the base excision repair/SSB repair pathway) or of ATM, DNA-PKcs, XRCC4, and Artemis (nonhomologous end-joining pathway) were determined at the 3 positions previously defined in the SOBP. Quantification of incident SSBs and DSBs by the alkaline elution technique and 3-dimensional (3D) immunofluorescence of γ-H2AX foci, respectively, was performed in SQ20 B cells. Results: We showed that the amount of SSBs and DSBs depends directly on the particle fluence and that the increase in relative biological efficiency observed in the distal part of the SOBP is due to a subset of lesions generated under these conditions, leading to cell death via a pathway in which the Artemis protein plays a centralmore » role. Conclusions: Because therapies like proton or carbon beams are now being used to treat cancer, it is even more important to dissect the mechanisms implicated in the repair of the lesions generated by these particles. Additionally, alteration of the expression or activity of the Artemis protein could be a novel therapeutic tool before high linear energy transfer irradiation treatment.« less
Authors:
 [1] ;  [2] ;  [2] ;  [1] ;  [3] ;  [4] ;  [1] ; ;  [3] ;  [2] ;  [3] ;  [2]
  1. Institut Curie Centre de Protonthérapie d'Orsay, Centre Universitaire, Orsay (France)
  2. (France)
  3. Institut Curie, Centre Universitaire, Orsay (France)
  4. Centre d'Etude Atomique, Direction des Sciences du Vivant, Institut des Maladies Emergentes et des Thérapies Innovantes, Service d'Etude des Prions et des Infections Atypiques, Fontenay-aux-Roses (France)
Publication Date:
OSTI Identifier:
22420406
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 90; Journal Issue: 1; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS; 62 RADIOLOGY AND NUCLEAR MEDICINE; APOPTOSIS; BIOLOGICAL PATHWAYS; BRAGG CURVE; CELL KILLING; DNA; EFFICIENCY; EXCISION REPAIR; HELA CELLS; ION BEAMS; LET; MATERIALS; MEV RANGE 10-100; NEOPLASMS; PROTON BEAMS; RADIOTHERAPY; STRAND BREAKS; THREE-DIMENSIONAL CALCULATIONS