, L'ensemble des résultats obtenus durant ces 3 années de thèse nous a permis d'établir la figure 81

, Ainsi, nous avons placé les informations obtenu via les expériences d'irradiations des cellules SW 1353 de CHS au sein de la « zone irradiée » tandis que les informations acquises via les expériences menées sur les cellules T/C-28a2 de chondrocytes au sein de la « zone non-irradiée ». Puis, par analogie avec les données de la littérature nous avons proposé des mécanismes qui pourraient expliquer en partie l'effet bystander radio, Ce schéma récapitulatif se positionne dans un contexte d'étude de l'effet bystander radio-induit lors du traitement d'un CHS

, Parmi ces facteurs bystander, nous avons pu identifier 3 cytokines candidates : l'IL-8, le TNF-? et MCP-1 qui pourraient être impliquées dans l'effet bystander. En effet, il est tout à fait envisageable que ces cytokines soient retrouvées au niveau de la zone non-irradiée et qu'elles se lient à la surface des cellules de chondrocytes qui possèdent les récepteurs à l'IL-8 (IL-8R), au TNF-? (TNFR) et à MCP-1 (CCR2). L'interaction de ces cytokines avec les cellules non-irradiées pourrait ainsi induire l'activation de voies métaboliques responsable des dommages à l'ADN, Ainsi ce schéma illustre la capacité des cellules de CHS après une irradiation à sécréter des facteurs bystander au sein de la zone irradiée

, La sécrétion d'IL-8 par les cellules de CHS irradiées pourrait s'expliquer par une augmentation de la CypA induite par l'irradiation. En effet, des études ont montré l'implication de la CypA dans la régulation de l'IL-8 (170). La CypA est également augmentée au sein des cellules de chondrocytes

. Ainsi, IL-8, nous pouvons suggérer qu'elle engendre la sécrétion par les cellules bystander d'IL-8, contribuant à la propagation de l'effet bystander radio-induit aux cellules voisines. Aussi, il est possible que des gap-jonctions soient formées entre les cellules T/C-28a2 adjacentes permettant ainsi un échange direct de facteurs comme l'IL-8 ou la CypA aux cellules voisines. Concernant les différentes voies métaboliques induite par l'interaction entre les cytokines et les cellules bystander, il semblerait que la voie de signalisation NF-?B qui, en sachant que cette protéine joue un rôle dans la régulation de l

. En, COX-2 a déjà été décrit pour son implication dans l'effet bystander radio-induit (97), notamment il semblerait que ce dernier soit impliqué dans la formation de ROS pouvant être responsable des dommages à l'ADN que nous avons observés (100). De plus, nous avons mis en évidence une diminution de l

, Enfin nos expériences nous ont également permis de mettre en évidence un retard de prolifération et

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