Analysis of the direct effects of ionizing radiation of different LETs in 3D reconstructed human articular cartilage and Chondrosarcoma models
Description
Hadron-therapy using carbon ions has many advantages due to physical and biological properties of this type of particle. Chondrosarcoma, a cartilaginous radio-resistant tumor, has been successfully treated using carbon ions. However, potential side effects to the surrounding healthy tissues are still poorly known. This project aims to study the direct effects of carbon ions in a 3D model of healthy articular cartilage and chondrosarcoma close to human homeostasis, in order to provide new tools for the evaluation of the relative biological effectiveness (RBE). The first part of the project was dedicated to the evaluation of carbon ions-induced impact on articular cartilage in the context of chondrosarcoma treatment. Compared to X-rays, the relative biological effectiveness of intermediate-LET carbon ions scored 2.6 in 2D monolayer culture. This was correlated with a stronger induction of cellular senescence. However, this differential effect was not reproduced using a 3D model of articular cartilage. Thus, the relative biological effectiveness of accelerated ions is probably overestimated using monolayer cultures (2D), compared to 3D. In the second part of this work, we developed a 3D chondrosarcoma model for hadron-biology studies. Protein extraction and immunohistochemistry protocols were developed. A new RBE evaluation method based on γ-H2AX repair kinetic in 3D, was proposed. (author)
Abstract (French)
L'hadrontherapie par ions carbone represente une modalite de radiotherapie alternative tres attractive du fait des proprietes physiques et biologiques de ce type de particules. Les chondrosarcomes, tumeurs radio-resistantes a differentiation cartilagineuse, sont en premiere ligne pour le traitement par ions carbone. Cependant, les effets secondaires sur les tissus sains environnants sont peu ou mal connus. Ce projet a pour but l'etude des effets directs des ions acceleres dans un modele 3D de cartilage sain et pathologique proche de l'homeostasie humaine et le developpement de nouveaux outils de calculs d'efficacite biologique relative (EBR). Dans un premier temps, nous nous sommes interesses aux sequelles radio-induites sur le cartilage articulaire dans un contexte d'hadrontherapie par ions carbone. En culture 2D physioxique (2% d'O2), l'efficacite biologique relative des ions carbone (transfert d'energie lineique ou TEL intermediaire) comparee aux rayons X a ete evaluee a 2,6. Ceci a ete correle a une plus forte induction de senescence radio-induite. Cependant, cet effet differentiel n'a pas ete retrouve en utilisant un modele 3D de cartilage articulaire. L'efficacite biologique relative des ions acceleres semble donc surevaluee, en utilisant des cultures en monocouche, par rapport a la 3D. Dans un deuxieme temps, un modele 3D de chondrosarcome a ete developpe pour des etudes d'hadronbiologie. Apres plusieurs obstacles techniques, des methodes d'extraction proteique et d'immunohistochimie ont ete mises au point. Une nouvelle methode d'evaluation de l'EBR en 3D basee sur la cinetique d'induction de la proteine γ-H2AX a ete proposee.
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Additional details
Additional titles
- Original title (French)
- Analyse des effets directs de rayonnements ionisants a differents TELs dans un modele experimental in vitro de cartilage humain sain et pathologique
Publishing Information
- Imprint Pagination
- 221 p.
- Report number
- FRCEA-TH--10104
INIS
- Country of Publication
- France
- Country of Input or Organization
- France
- INIS RN
- 50046557
- Subject category
- S63: RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS; S62: RADIOLOGY AND NUCLEAR MEDICINE;
- Resource subtype / Literary indicator
- Thesis
- Descriptors DEI
- CARBON IONS; CARTILAGE; HADRONS; HOMEOSTASIS; RADIOTHERAPY; RBE; SARCOMAS
- Descriptors DEC
- ANIMAL TISSUES; BODY; CHARGED PARTICLES; CONNECTIVE TISSUE; DISEASES; ELEMENTARY PARTICLES; IONS; MEDICINE; NEOPLASMS; NUCLEAR MEDICINE; RADIOLOGY; THERAPY
Optional Information
- Notes
- 172 refs.; Available from the INIS Liaison Officer for France, see the INIS website for current contact and E-mail addresses; Also available from Le Service Commun de la Documentation de l'universite Paris-Sud, Domaine universitaire de Paris-Sud Batiment 407 Rue du Doyen Georges Poitou 91405 ORSAY Cedex (France)