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

Abstract

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. Electronic supplementary material The online version of this article (10.1007/s12079-019-00515-9) contains supplementary material, which is available to authorized users.

Hadrontherapy Interactions in Molecular and Cellular Biology

“…Differences in RIBEs have been observed between x-ray, gamma-ray irradiation, and hadrontherapy with carbon ions. Although the RBE is 2-3 times higher for carbon ions versus x-rays, the RIBEs are similar in magnitude [86,87].…”

“…A bystander effect was observed when transferring the conditioned medium of irradiated chondrosarcoma cells to chondrocytes, but the reduction in proliferation was lower with C-ions compared with x-rays at the same doses [86]. In contrast, in bystander cells, the induction of micronuclei and cell death increased with LET when conditioned medium from irradiated cells was transferred to bystander cells deficiencies in DNA repair [88].…”

“…RIBEs increase intercellular communication between irradiated and nonirradiated cells and appear to be LET-dependent [89,91]. Because RIBEs might be lower with high-LET irradiation [86], further data on RIBEs with hadrontherapy (high-and low-LET) versus x-rays are needed.…”

Ionizing radiation exposure of stem cell-derived chondrocytes affects their gene and microRNA expression profiles and cytokine production

“…Lepleux et al 18 found that the radiation-induced bystander response can be transferred from chondrosarcoma cells treated with IR to non-irradiated chondrocyte cells. A great impact on chondrocyte survival was observed at low doses.…”

“…Bystander factors secreted in the conditioned medium contributed to the reduced proliferation and elevated DNA damage level at low doses (X-rays and C-ions). Bystander biological activity was absent after dilution and heat treatment of the conditioned medium, leading the authors to suggest that factors such as TNF-α and IL-6 may have contributed to this effect 18 .…”