Differential effects of irradiation with X‐Rays and carbon ions on normal and tumoral uveal melanocytes

Abstract

AbstractPurpose The local treatment of uveal melanoma (UM) proposed is in the majority of the cases the protontherapy or the radiotherapy of contact by patches. However, these treatment ends in blindness in 60 % of the cases. Indeed, the hadrons which are proton and carbon ion possess a Transfer of Linear Energy (LET) higher than the conventional radiotherapy (X‐rays and γ). Our previous findings highlight the key role of the WTB‐Raf/MEK/ERK pathway in the control of proliferation of UM cells. Our project investigate the positive and negative effects of the irradiation on the UM and healthy uveal melanocytes. It thus seems interesting to analyze the effects of the irradiation on ERK1/2 activation and the link between these pathways with the cell cycle.Methods We characterize the radiosensibilities, after irradiation by X‐rays and carbon ion, of six UM cell llines (92.1, Mel 270, SP6.5, MKT‐Br, µ2 and TP17) and two types of healthy cells: the human uveal melanocytes (NUM) and the epithelial cells of the human retina (ARPE19).Results We showed that carbon ion present with regard to the X‐rays a relative biological effectiveness (RBE) of 1.86 to 2.46 at 10% survival. We showed that the irradiations X and carbon had the same effects by provoking a stop of the cellular cycle in phase G2 / M until 120 hours. According to the type of irradiation, two mechanisms are observed on the ERK1/2 signaling pathway. X‐ray induced a transitory suractivation of ERK1/2. Whereas, ERK1/2 activation was constantly inhibited by carbon beamConclusion These preliminary results show that the carbon beam present a better biological efficiency than X‐rays in uveal melanoma cells leading a sustain inhibition of ERK1/2 pathway.