Bystander Effectors of Chondrosarcoma Cells Irradiated at Different Let Impair Proliferation of Chondrocytes

Abstract

Radiation-induced bystander effects (RIBE) describe non-targeted cellular responses in non-irradiated cells influenced by signals from irradiated neighbors. Although documented in various systems, their mechanisms in chondrosarcoma–chondrocyte interactions, especially under high linear energy transfer (LET) radiation, remain poorly understood. This study evaluated and compared the direct and bystander responses of human chondrocytes (T/C-28a2) exposed to factors released by irradiated human chondrosarcoma cells (SW1353) using low-LET X-rays and high-LET carbon ions (C-ions). SW1353 cells were irradiated with 0.05–8 Gy of X-rays or C-ions, and conditioned medium was transferred to non-irradiated T/C-28a2 cells. Endpoints included clonogenic survival, proliferation (impedancemetry), DNA damage (micronucleus assay), and cytokine profiling. The effects of conditioned medium dilution and heat treatment were also examined. Low doses (0.1 Gy X-rays, 0.05 Gy C-ions) elicited maximal bystander effects, reducing chondrocyte survival to 36% and 62%, respectively. DNA damage was significantly increased at these doses. Dilution ≥50% or heating to ≥70 °C abolished bystander effects. TNF-α and IL-6 were identified as key   cytotoxic and genotoxic effects in chondrocytes at low radiation doses. These findings highlight the clinical need to consider RIBE in high-precision therapies.