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Variation of 4 MV X-ray dose rate strongly impacts biological response both in vitro and in vivo
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Edité par CCSD ; Nature Publishing Group -
International audience. Based on classic clonogenic assay, it is accepted by the scientific community that, whatever the energy or the dose rate, the relative biological effectiveness of X-rays is equal to 1. However, although X-ray beams are widely used in diagnosis, interventional medicine and radiotherapy, comparisons of their dose rates are scarce. We therefore assessed in vitro the effects of high-energy X-rays at two dose rates (0.63 and 2.5 Gy/min) using normal endothelial cells (HUVECs) by using clonogenic assay, measuring viability/mortality, studying the cell cycle and cellular senescence by flow cytometry and by performing gene analysis on custom arrays. In order to consolidate these data, we performed localized irradiation of exteriorized small intestine at 0.63 and 2.5 Gy/min. Interestingly, in vivo validation has shown a significantly higher loss of weight at the higher dose when irradiating to 19 Gy a small fragment of exteriorized small intestine of C57Bl6J mice. Nevertheless, no significant differences were observed in lesioned scores between the two dose rates, while bordering epithelium staining indicated twofold greater severe damage at 2.5 Gy/min compared to 0.63 Gy/min at one week post-irradiation. Taken together, these experiments systematically show more adverse effects of high energy X-rays at 2.5 Gy/min, while the relative biological effectiveness of photons is around 1, whatever the quality of the X-ray beam. These results strongly suggest that multiparametric analysis should be considered in support of clonogenic assay.
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