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Bystander Effects of human chondrosarcoma cells irradiated with accelerated ions
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Edité par CCSD -
International audience. For the treatment of cancer resistant to conventional radiotherapy, hadrontherapy with carbon ions seems to be a good alternative. Hadrontherapy uses accelerated ions; this technique is interesting when the tumor is deep and isolated or located close to sensible organs. Indeed, the dose deposit is maximal within the tumor volume (Bragg pick), and minimal before and after the tumor, preserving the surrounding healthy tissues. Chondrosarcoma is a good candidate for hadrontherapy because this cancer is radio and chemo resistant, and can be un-operable, when located in the skull base. However, it is necessary to evaluate the secondary effects of this irradiation type, especially the interaction between irradiated and non-irradiated cells. Among these effects, the radiation-induced bystander effect involves stress signals emitted by irradiated cells adjacent or very close to non-irradiated cells; bystander molecules can induce a biological response with damages usually observed with irradiated cells [1,2]. To study this phenomenon, we used a protocol of medium transfer. Cells are irradiated with X-rays or carbon ions and then the bystander supernatant, containing the signals emitted by irradiated cells, is transferred on non-irradiated cells. Chondrosarcoma cells and chondrocytes were analyzed as emitting and/or receptor cells of bystander signals. We use different technical strategies to study the survival cells fraction after treatment, the DNA damages and to identify of bystander factors. Our results showed a significant reduction of chondrocyte survival after transfer of conditioned medium from chondrosarcoma cells irradiated with low doses of X-Rays and C-ions. By diluting this medium, the phenomenon decreased proportionally, confirming the presence of bystander factors. Some of these factors were partially observed using multiplex analysis of cell cytokines. Taken together, these results showed the capacity of chondrosarcoma cells to secrete bystander signals, particularly at low irradiation dose, and the capacity of chondrocyte cells to receive these signals. Even if in vivo experiments are still required, these results open the discussion with the medical staff for protocol adaptations during radiotherapy, in order to limit the damaging impact of bystander effect within the healthy tissues.
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