High LET Radiation Overcomes In Vitro Resistance to X-Rays of Chondrosarcoma Cell Lines

François Chevalier (1) , Dounia Houria Hamdi , Charlotte Lepleux (1) , Mihaela Temelie (1) , Anaïs Nicol (2) , Jean Baptiste Austry (1) , Paul Lesueur (3) , Guillaume Vares (4) , Diana Savu (5) , Tetsuo Nakajima (4) , Yannick Saintigny (1)

1 LARIA - Laboratoire d'Accueil et de Recherche avec les Ions Accélérés
2 CRLCC Paul Strauss - Centre Paul Strauss
3 UNICANCER/CRLC - Centre Régional de Lutte contre le Cancer François Baclesse [Caen]
4 National Institute of Radiobiological Sciences
5 Department of Life and Environmental Physics [Magurele, Roumanie]

Chondrosarcomas are malignant tumors of the cartilage that are chemoresistant and radioresistant to X-rays. This restricts the treatment options essential to surgery. In this study, we investigated the sensitivity of chondrosarcoma to X-rays and C-ions in vitro. The sensitivity of 4 chondrosarcoma cell lines (SW1353, CH2879, OUMS27, and L835) was determined by clonogenic survival assays and cell cycle progression. In addition, biomarkers of DNA damage responses were analyzed in the SW1353 cell line. Chondrosarcoma cells showed a heterogeneous sensitivity toward irradiation. Chondrosarcoma cell lines were more sensitive to C-ions exposure compared to X-rays. Using D10 values, the relative biological effectiveness of C-ions was higher (relative biological effectiveness ¼ 5.5) with cells resistant to X-rays (CH2879) and lower (relative biological effectiveness ¼ 3.7) with sensitive cells (L835). C-ions induced more G2 phase blockage and micronuclei in SW1353 cells as compared to X-rays with the same doses. Persistent unrepaired DNA damage was also higher following C-ions irradiation. These results indicate that chondrosarcoma cell lines displayed a heterogeneous response to conventional radiation treatment; however, treatment with C-ions irradiation was more efficient in killing chondrosarcoma cells, compared to X-rays.

Mots clés: radiation-resistance; sarcoma; relative biological effectiveness; C-ions; 2D culture; DNA damage response Abbreviations ANOVA; analysis of variance; CSDs; colony size distributions; EdU; 5-ethynyl-2 0 -deoxyuridine; GANIL; Grand Accelérateur National d'Ions Lourds; HIMAC; Heavy Ion Medical Accelerator in Chiba; LET; linear energy transfer; MEM; minimum essential medium Eagle; PBS; phosphate buffered saline; PMMA; poly-methyl methacrylate; RBE

Domaines: Cancer; Médecine nucléaire

François Chevalier, Dounia Houria Hamdi, Charlotte Lepleux, Mihaela Temelie, Anaïs Nicol, et al.. High LET Radiation Overcomes In Vitro Resistance to X-Rays of Chondrosarcoma Cell Lines. Technology in Cancer Research and Treatment, 2019, 18, pp.153303381987130. ⟨10.1177/1533033819871309⟩. ⟨hal-02333914⟩