Radiation-induced DNA damage response of hematopoietic stem cells after proton irradiation

Leukemia is the most important malignancy after radiation exposure during childhood. The high risk of developing leukemia is related to the high sensitivity of the bone marrow, which harbors hematopoietic stem and progenitor cells (HSPCs). In the field of radiotherapy, proton therapy has become a focus of attention the last few years. Protons are particularly useful to treat tumors located close to radiosensitive tissues and in anatomical sites where surgical access is limited, e.g. for brain tumors. The significant decrease of dose to non-target tissues compared to standard X-ray therapy is particularly important for pediatric patients. The high radiosensitivity of children with respect to radiation-induced leukemia warrants studies on the response of HSPCs to radiation-induced DNA damage as well as on the mutagenic consequences of DNA misrepair. Currently, there is little information available on the response of HSPCs to proton therapy and this study aims to elucidate the response of HSPCs (CD34+) to clinical therapy beams of different radiation qualities. To test the radiosensitivity of the HSPCs and investigate radiation-induced DNA damage in these stem cells, we performed the cytokinesis block micronucleus (CBMN) assay after irradiation with photons (X-rays) or protons. Dose-response curves for both types of irradiation were compared and the differences in biological effect were analysed.