IMR Press / FBL / Volume 27 / Issue 9 / DOI: 10.31083/j.fbl2709277
Open Access Original Research
Label-Free Direct Mass Spectrometry Analysis of the Bystander Effects Induced in Chondrocytes by Chondrosarcoma Cells Irradiated with X-rays and Carbon Ions
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1 UMR6252 CIMAP, team Applications in Radiobiology with Accelerated Ions, CEA - CNRS - ENSICAEN - University de Caen Normandie, 14000 Caen, France
2 Plateforme Proteogen, US EMerode, Université de Caen Normandie, 14000 Caen, France
3 University Grenoble Alpes, CEA, CNRS, IRIG-LCBM-UMR5249, 38054 Grenoble, France
*Correspondence: chevalier@ganil.fr; francois.chevalier@cea.fr (François Chevalier)
Academic Editor: Graham Pawelec
Front. Biosci. (Landmark Ed) 2022, 27(9), 277; https://doi.org/10.31083/j.fbl2709277
Submitted: 22 July 2022 | Revised: 13 September 2022 | Accepted: 22 September 2022 | Published: 30 September 2022
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract

Background: Radiation-induced bystander effects are induced changes in cells that were not themselves directly irradiated but were in the vicinity of a radiation path. Such effects, which occur in the microenvironment of an irradiated tumor, remain poorly understood and depend on the cell type and irradiation quality. This study aimed to evaluate bystander effects in non-irradiated chondrocytes that received conditioned medium from irradiated chondrosarcoma cells. Methods: SW1353 chondrosarcoma cells were irradiated with X-rays and carbon ions, each at 0.1 Gy and 2 Gy, and the conditioned media of the irradiated cells were transferred to T/C-28A2 chondrocytes and Human Umbilical Venous Endothelial Cells (HUVECs). The whole proteome of bystander chondrocytes was analyzed by label-free mass spectrometry, and a comparative study was performed by dose and irradiation quality. HUVECs were evaluated for inflammatory cytokine secretion. Results: The bystander response of chondrocytes to X-ray irradiation primarily affected the protein translation pathway (DHX36, EIF3B, EIF3D, EIF3M, EIF5, RPL6, RPLP0, RPS24, SYNCRIP), IL-12 (AIP, BOLA2, MIF, GAS6, MIF, PDGFRB) and the oxidative stress pathway (MGST3, PRDX2, PXDN, SOD2, TXN, TXNL1). Following carbon-ion irradiation, the G1/S pathway (PCBP4, PSMD12, PSME, XIAP) and mitotic G2 DNA damage checkpoint pathway (MRE11, TAOK1, UIMC1) were engaged. Changes in the regulation of chromosome separation (BCL7C, BUB3, CENPF, DYNC1LI1, SMARCA4, SMC4) 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 proteins. Stress granules were significantly enriched according to an interaction map. Conclusions: All these accessions corresponded to a window of the proteins modulated in response to the bystander effect. Our chondrosarcoma model clarified the nature of the bystander response of chondrocytes and may suggest several interesting new mechanisms that are specific to particular irradiation doses and qualities.

Keywords
bystander effect
carbon irradiation
chondrosarcoma
proteomic analysis
stress granules
IL12
Funding
ANR‐10‐EQPX‐1401/Agence Nationale de la Recherche
ANR-17-EURE-0003/Chemistry Biology Health (CBH) Graduate School of University Grenoble Alpes
ANR-11-LABX-0063/LABEX PRIMES
Figures
Fig. 1.
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