title: Comparable Senescence Induction in Three-dimensional Human Cartilage Model by Exposure to Therapeutic Doses of X-rays or C-ions.
abstract: OBJECTIVE
  Particle therapy using carbon ions (C-ions) has been successfully used in the treatment of tumors resistant to conventional radiation therapy. However, the potential side effects to healthy cartilage exposed to lower linear energy transfer (LET) ions in the beam track before the tumor have not been evaluated. The aim of the present study was to assess the extent of damage after C-ion irradiation in a 3-dimensional (3D) cartilage model close to human homeostasis.
  
  
  METHODS
  Primary human articular chondrocytes from a healthy donor were cultured in a collagen scaffold to construct a physioxic 3D cartilage model. A 2-dimensional (2D) culture was used as a reference. The cells were irradiated with a single dose of a monoenergetic C-ion beam with a LET of approximatively 30 keV/μm. This LET corresponds to the entrance channel of C-ions in the shallow healthy tissues before the spread-out Bragg peak (∼100 keV/μm) during hadron therapy protocols. The same dose of X-rays was used as a reference. Survival, cell death, and senescence assays were performed.
  
  
  RESULTS
  As expected, in the 2D culture, C-ions were more efficient than X-rays in reducing cell survival with a relative biological effectiveness of 2.6. This correlated with stronger radiation-induced senescence (two-fold) but not with higher cell death induction. This differential effect was not reflected in the 3D culture. Both ionizing radiation types induced a comparable rate of senescence induction in the 3D model.
  
  
  CONCLUSIONS
  The greater biological effectiveness of C-ions compared with low LET radiation when evaluated in treatment planning systems might be misevaluated using 2D culture experiments. Radiation-induced senescence is an important factor of potential cartilage attrition. The present data should encourage the scientific community to use relevant models and beams to improve the use of charged particles with better safety for patients.
authors.affiliation: Laboratoire d'Accueil et de Recherche avec les Ions Accélérés (LARIA), Institut de Radiobiologie Cellulaire et Moléculaire (IRCM), Direction de la Recherche Fondamentale (DRF), Commissariat à l'Energie Atomique et aux Energies Alternatives, Caen, France.
authors.forename: Dounia Houria
authors.initials: DH
authors.lastname: Hamdi
authors.affiliation: Laboratoire d'Accueil et de Recherche avec les Ions Accélérés (LARIA), Institut de Radiobiologie Cellulaire et Moléculaire (IRCM), Direction de la Recherche Fondamentale (DRF), Commissariat à l'Energie Atomique et aux Energies Alternatives, Caen, France.
authors.forename: François
authors.initials: F
authors.lastname: Chevalier
authors.affiliation: UMR6249, Université de Franche-Comté, Besançon, France.
authors.forename: Jean-Emmanuel
authors.initials: JE
authors.lastname: Groetz
authors.affiliation: UMR6252, Centre de Recherche sur les Ions, les Matériaux et la Photonique (CIMAP), Direction de la Recherche Fondamentale (DRF), Commissariat à l'Energie Atomique et aux Energies Alternatives, Caen, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Durantel
authors.affiliation: FRE3377, Service de Biologie Intégrative et Génétique Moléculaire (SBIGeM), Institut de Biologie et de Technologies de Saclay (iBiTec-S), Direction de la Recherche Fondamentale (DRF), Commissariat à l'Energie Atomique et aux Energies Alternatives, Gif-sur-Yvette, France and Institut de Biologie Intégrative de la Cellule (I2BC) / Université Paris Saclay, Gif-sur-Yvette, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Thuret
authors.affiliation: FRE3377, Service de Biologie Intégrative et Génétique Moléculaire (SBIGeM), Institut de Biologie et de Technologies de Saclay (iBiTec-S), Direction de la Recherche Fondamentale (DRF), Commissariat à l'Energie Atomique et aux Energies Alternatives, Gif-sur-Yvette, France and Institut de Biologie Intégrative de la Cellule (I2BC) / Université Paris Saclay, Gif-sur-Yvette, France.
authors.forename: Carl
authors.initials: C
authors.lastname: Mann
authors.affiliation: Laboratoire d'Accueil et de Recherche avec les Ions Accélérés (LARIA), Institut de Radiobiologie Cellulaire et Moléculaire (IRCM), Direction de la Recherche Fondamentale (DRF), Commissariat à l'Energie Atomique et aux Energies Alternatives, Caen, France. Electronic address: yannick.saintigny@cea.fr.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Saintigny
mesh_terms: D001859:Bone Neoplasms / Q000532:radiotherapy; D002244:Carbon; D002356:Cartilage / Q000166:cytology / Q000528:radiation effects*; D018929:Cell Culture Techniques; D016923:Cell Death; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D016922:Cellular Senescence; D019902:Chondrocytes / Q000528:radiation effects*; D002813:Chondrosarcoma / Q000532:radiotherapy; D063193:Heavy Ion Radiotherapy / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D018499:Linear Energy Transfer; D011832:Radiation Injuries / Q000150:complications*; D012062:Relative Biological Effectiveness; D014965:X-Rays
chemical_list: D002244:Carbon