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