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AbstractAbstract
[en] In conventional radiotherapy (X-ray) or unconventional radiotherapy (Hadron therapy), the impact of irradiation on healthy tissue raises essential questions of radiobiology, these healthy tissues being in the path of the beam during the treatment of a patient tumor. Among these questions, what is the impact of the radio-induced Bystander effect? This mechanism involves stress signals still poorly identified, emitted by one or more irradiated cells to adjacent or very close non-irradiated cells, which can produce biological effects close to those obtained in the irradiated zone. To study this phenomenon, we used various molecular biology techniques including: clonogenic assay to study the survival fraction of cells after treatment, two-dimensional electrophoresis allowing the analysis of the cellular proteome, conditioned medium analysis for identify Bystander signals emitted by irradiated cells and proteomembrane experiments aimed at studying cells in a mix. In parallel with these study techniques, we have developed a 3D cell culture model via the use of 'pellets' (cell aggregates). Our results showed a decrease in the survival of bystander cells after transfer of medium from irradiated cells, the potential involvement of some cytokines in bystander signaling as well as several candidate proteins that may partly explain the bystander response. (author)
[fr]
Lors d'une radiotherapie conventionnelle (Rayons X) ou non-conventionnelle (Hadrontherapie), l'impact des irradiations sur les tissus sains pose des questions essentielles de radiobiologie, ces tissus sains se trouvant sur le trajet du faisceau lors du traitement d'une tumeur. Parmi ces questions, quel est l'impact de l'effet Bystander radio-induit? Ce mecanisme fait intervenir des signaux de stress encore mal identifies, emis par une ou plusieurs cellules irradiees vers les cellules non irradiees adjacentes ou tres proches, pouvant produire des effets biologiques proches de ceux obtenus dans la zone irradiee. Afin d'etudier ce phenomene, nous avons utilise differentes techniques de biologie moleculaire dont: des tests de clonogenicite permettant d'etudier la survie des cellules apres un traitement, des electrophoreses bidimensionnelles permettant l'analyse du proteome cellulaire, des analyses de milieux conditionnes permettant d'identifier les signaux Bystander emis par les cellules irradiees et des experiences de proteo-genomique visant a etudier des cellules en melange. En parallele de ces techniques d'etude, nous avons developpe un modele de culture de cellules en 3D via l'utilisation de 'pellets' (agregats cellulaires). Nos resultats ont montre une diminution de la survie des cellules bystander apres transfert de milieu provenant de cellules irradiees, l'implication potentiel de certaines cytokines dans la signalisation bystander ainsi que plusieurs proteines candidates pouvant expliquer en partie la reponse bystander.Original Title
Etude des signaux bystander emis par des cellules de cartilage cultivees en 3D et irradiees in vitro dans un contexte de radiotherapie conventionnelle et d'Hadrontherapie
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2 Nov 2018; 213 p; 191 refs.; Available from the INIS Liaison Officer for France, see the INIS website for current contact and E-mail addresses; Aspects Moleculaires et Cellulaires de la Biologie
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Report
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Thesis/Dissertation
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