Bystander communication between irradiated chondrosarcoma cells and non-irradiated chondrocytes: proteomic study according to doses and LETs

A Gilbert (1) , M Tudor (2) , D Savu (2) , S Candéias (3) , François Chevalier (1, 4, 5)

1 ARIA - Accueil et Recherche en Radiobiologie des Ions Accélérés
2 Horia Hulubei National Institute for Physics and Nuclear Engineering
3 LCBM - UMR 5249 - Laboratoire de Chimie et Biologie des Métaux
4 IRAMIS - Institut Rayonnement Matière de Saclay (DRF)
5 CIMAP - UMR 6252 - Centre de recherche sur les Ions, les MAtériaux et la Photonique

Chondrosarcomas are malignant tumors of the cartilage that are chemoresistant and radioresistant to X-rays. This restricts the treatment options essential to surgery. Hadrontherapy with carbon ions (C-ions) presents several advantages when compared with conventional radiotherapy (X-rays), including a reduced dose in healthy tissues (Bragg peak) and an increased biological effect (RBE= 2.5 to 3). This modality of treatment is promising for chondrosarcoma treatment improvement. Considerable evidence has accumulated showing that irradiations can induce a biological response in non-irradiated cells that are in proximity to irradiated cells. This radiation-induced bystander effect is mainly dependent of the cell type, and treatment (irradiation quality, dose, time of contact…). In vitro, we observed a non-targeted effect using a medium transfer protocol, with a reduction of the survival fraction of bystander cells and an increase in micronuclei, especially at low doses1. Following this cellular observation, we analyzed the cellular mechanisms and we studied the factors involved in this bystander effect, using proteomic analysis strategies1,2. Proteins involved in stress granules and several proteins involved in the cellular response to DNA damage stimuli were increased in the conditioned medium of 0.1 Gy irradiated samples3. The metabolism of bystander cells is also impacted: changes in the regulation of chromosome separation were associated with only low dose X-ray and carbon-ion irradiation; modification of the protein translation pathway represented at least 30% of bystander effects and could play a role, possibly along with stress granules, in reduction in cellular metabolism to protect proteins4. Our in vitro model helps to clarify the nature of the bystander response of chondrocytes located near irradiated chondrosarcoma cells and may suggest several interesting new mechanisms that are specific to irradiation doses and qualities. References

Domaines: Sciences du Vivant [q-bio]

A Gilbert, M Tudor, D Savu, S Candéias, François Chevalier. Bystander communication between irradiated chondrosarcoma cells and non-irradiated chondrocytes: proteomic study according to doses and LETs. ICRR2023 - the 17th International Congress for Radiation Research, Aug 2023, Montréal, Canada. . ⟨hal-04217083⟩