2022-07-01 16:21


Conference: Bucharest University Faculty of Physics 2019 Meeting

Section: Biophysics; Medical Physics

Direct and bystander effects of human chondrosarcoma irradiated with protons

Mihaela TUDOR (1), Mihaela TEMELIE (1), Liviu CRACIUN (1) and Diana SAVU (1)

1) Horia Hulubei National Institute for R&D in Physics and Nuclear Engineering (IFIN-HH)


Radiation-induced bystander effect, Chondrosarcoma, DNA damage, Protons

Ionizing radiation induces complex cellular effects in irradiated cells as well as never irradiated “bystander” cells which have received signals produced by irradiated cells. Characterising both direct and non-targeted bystander effects may make important contributions to overall outcome of radiation exposure which could have implications in radiotherapy and radioprotection. In this study we focused on analysing direct and bystander cellular effects of proton irradiation of chondrosarcoma cells. Chondrosarcoma is resistant towards conventional chemo-/radiotherapy and can be un-operable. Radiotherapy using charged particles (hadron therapy) is now a good alternative for chondrosarcoma. The advantages of this method include higher specificity (given by it’s specific Bragg pick) and increased biological efficacy (due to the high LET). Still, the adverse effects of hadron therapy cannot be neglected. We used an in vitro model consisting of proton-irradiated (0.1-2 Gy) chondrosarcoma cells (SW1353). We used a proton beam line generated by the TR19 Cyclotron of IFIN-HH. To study the bystander phenomena we used a medium transfer protocol. The bystander supernatant containing signals emitted by proton irradiated chondrosarcoma cells, was transferred to non-irradiated bystander normal chondrocyte (T/C-28a2) and endothelial (EA.hy926) cells. Cell survival and DNA damage were quantified in directly irradiated chondrosarcoma cells and in bystander chondrocyte and endothelial cells. A dose dependent direct effect was observed in chondrosarcoma cells as increased number of micronuclei and a decrease in long-term cellular survival following irradiation. After receiving the conditioned bystander medium, the bystander cells also showed a significant reduction of survival and an increased MN formation but the effects are less pronounced than in the case of directly irradiated chondrosarcoma cells. Our results showed that proton-irradiated chondrosarcoma cells have the ability to release stress factors inducing bystander responses in the non-irradiated surrounding chondrocyte/endothelial cells.

We acknowledge the Romanian Ministry of Research and Innovation: PN 19060203/2019, 36 PFE/2018, 18PCCDI/2018.