Differential Radiosensitivity of Uveal Melanoma Cell Lines After X-rays or Carbon Ions Radiation

We compared the radiosensitivity of uveal melanoma (UM) cell lines after x-ray or carbon-ions radiation (C-ions).

We characterized the radiosensitivity toward x-rays and C-ions of UM cell lines: 92.1, MEL270, SP6.5, MKT-BR, μ2, and TP17. Normal choroidal melanocytes and the retinal pigment epithelial cell line ARPE19 were used as controls for normal cells. X-rays were delivered with an energy of 6 MV at a dose rate of 2 Gy/min. X-rays served as a reference for Relative Biological Effectiveness (RBE) evaluation. Radiation with C-ions was delivered at 75 MeV/u (34 keV/μm) at a dose rate of 2 Gy/min. After single-doses (0-8 Gy) of medical x-rays (6 MV) or C-ions (33 keV/μm), cells sensitivity was measured using standard colony formation assay, and cell growth was examined by counting the cell colonies. The effect of x-rays or C-ions on the expression and activation of ERK1/2 was evaluated by Western Blot.

C-ions presented with regard to the x-rays a RBE of 1.9 to 2.5 at 10% of UM cells survival. The x-ray sensitivity of UM cells was neither influenced by the synchronization of cells in phase G0/G1 of the cell cycle nor by the level of oxygenation. X-ray and C-ions radiation had the same effects on cell cycle leading to a mitotic catastrophe that appeared earlier after C-ions than x-ray treatment. However, C-ions radiation induced a sustained inhibition of ERK1/2 activation compared to the transitory induction of that signalization pathway after x-ray radiation.

This in vitro study shows that C-ions had a better biological effectiveness than x-rays leading to a sustained inhibition of the ERK1/2 pathway.