Abstract
Purpose: :
The purpose of our study is to investigate the irradiation effects of carbon ions (C-ions) and X-rays on the uveal melanoma (UM) and healthy melanocytes with different culture conditions.
Methods: :
We characterized the radio-sensibilities of six UM cell lines (92.1, Mel 270, SP6.5, MKT-Br, μ2 and TP17) and two types of healthy cells: the human normal choroidal melanocytes (NCM) and the epithelial cells of the human retina (ARPE19). The sensitivity of cells was measured after irradiation by C-ions or X-Rays using standard colony formation assay and curves were fitted according the linear quadratic model. For X-rays we compared the results obtained with cells in exponential growth phase and those obtained with confluent cells. We also compared the one obtained in normoxia with those obtained in hypoxia with 1% of O2. To compare C-ions and X-Rays, we selected D37 and D10, the doses required to reduce the surviving fraction to 37% and 10% respectively and calculated the Relative Biological Effectiveness (RBE).
Results: :
Although radiation therapy is used in clinical practice to treat UM, our results showed UM cell lines are radioresistant after a single dose of X-ray with cells cultured in exponential growth phase in normoxia. The culture growth phase did not induce any statistically significant difference on the radiosensitivity with X-rays. Hypoxia induce a slowing down of cell proliferation but did not induce any statistically significant difference on the radiosensitivity. UM cell lines are more radiosensitive with C-ions than with X-Rays with RBE values between 1.9 and 2.6 depending of the cell line and the surviving fraction.
Conclusions: :
UM is a radioresistant tumor treated in clinical practice with high doses of X-Rays to overcome this radioresistance. The environmental factors like culture growth phase and hypoxia do not induce any change on UM cell line radiosensitivity. C-ions are more efficient than X-rays, especially with the more radioresistant UM cell lines like Mkt-Br and could therefore be used to avoid tumor progression. With this particularly efficient form of radiotherapy, we could also discuss the use of lower doses to avoid secondary effect of radiation therapy.
Keywords: melanoma • radiation therapy • hypoxia