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J Cell Commun Signal. 2019 Sep;13(3):343-356. doi: 10.1007/s12079-019-00515-9. Epub 2019 Mar 22.

Bystander effectors of chondrosarcoma cells irradiated at different LET impair proliferation of chondrocytes.

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LARIA, iRCM, François Jacob Institute of biology, DRF-CEA, Caen, France.
UMR6252 CIMAP, CEA - CNRS - ENSICAEN - Université de Caen Normandie, Caen, France.
Department of Life and Environmental Physics, Horia Hulubei National Institute of Physics and Nuclear Engineering, Reactorului 30, P.O. Box MG-6, 077125, Magurele, Romania.
ImpedanCELL Platform, Federative Structure 4206 ICORE, Normandie Univ, UNICAEN, Inserm U1086 ANTICIPE « Interdisciplinary Research Unit for Cancer Prevention and Treatment », Biology and Innovative Therapeutics for Ovarian Cancers group (BioTICLA), Comprehensive Cancer Center F. Baclesse, 14000, Caen, France.
Research Division, Hospital for Special Surgery and Weill Cornell Medical College, New York, NY, USA.
University of Montpellier, LBPC/PPC, IRMB, CHU de Montpellier, 34000, Montpellier, France.
Cell Signal Unit, OIST, Onna-son, Okinawa, Japan.
Dept. of Radiation Effects Research, NIRS, QST, Chiba-shi, Japan.
LARIA, iRCM, François Jacob Institute of biology, DRF-CEA, Caen, France.
UMR6252 CIMAP, CEA - CNRS - ENSICAEN - Université de Caen Normandie, Caen, France.


While the dose-response relationship of radiation-induced bystander effect (RIBE) is controversial at low and high linear energy transfer (LET), mechanisms and effectors of cell-to-cell communication stay unclear and highly dependent of cell type. In the present study, we investigated the capacity of chondrocytes in responding to bystander factors released by chondrosarcoma cells irradiated at different doses (0.05 to 8 Gy) with X-rays and C-ions. Following a medium transfer protocol, cell survival, proliferation and DNA damages were quantified in bystander chondrocytes. The bystander factors secreted by chondrosarcoma cells were characterized. A significant and major RIBE response was observed in chondrocyte cells (T/C-28a2) receiving conditioned medium from chondrosarcoma cells (SW1353) irradiated with 0.1 Gy of X-rays and 0.05 Gy of C-ions, resulting in cell survivals of 36% and 62%, respectively. Micronuclei induction in bystander cells was observed from the same low doses. The cell survival results obtained by clonogenic assays were confirmed using impedancemetry. The bystander activity was vanished after a heat treatment or a dilution of the conditioned media. The cytokines which are well known as bystander factors, TNF-α and IL-6, were increased as a function of doses and LET according to an ELISA multiplex analysis. Together, the results demonstrate that irradiated chondrosarcoma cells can communicate stress factors to non-irradiated chondrocytes, inducing a wide and specific bystander response related to both doses and LET.


Chondrocyte; Chondrosarcoma; High-LET; Low-dose irradiation; Radiation-induced bystander effect

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