DNA Double-Strand Breaks and Individual Response in Radiodiagnosis

The evaluation of the potential risks of radiation low doses is an important societal issue. Low doses are generally delivered in very different conditions with various physical characteristics, making this evaluation more complex. Dose values, dose rate, number of irradiations and time between exposures may significantly impact the biological and clinical response. To date, radiodiagnosis procedures, notably CT scan exams, represent the largest cause of medical exposure to ionizing radiation (IR). In parallel, epidemiological studies are showing an increase incidence of cancers after CT scan exposure, especially for children. However, this studies are limited due to retrospective assessment of radiation dose from CT scans, indication bias, and lack of statistical power. Furthermore, although it is still not included in the International Radiation Protection Recommendations yet, individual radiosensitivity appears to be an unavoidable factor to consider in any radiation-induced risk evaluation. This is why the contribution of radiobiology is essential to complete our knowledge on low doses in clinical situations by considering the individual factor. Since 2016, a unified model of the individual response to IR relevant to both high and low doses and based on the radiation-induced nucleo shuttling of the ATM protein kinase (RIANS) has been proposed. In the frame of the RIANS model, IR trigger the monomerization of the ATM dimeric forms in cytoplasm. The resulting ATM monomers diffuse in nucleus and phosphorylate the H2AX histone variant molecular (γH2AX) at DSB sites, which triggers the formation of nuclear γH2AX foci, quantifiable by immunofluorescence. The ATM-dependent formation of γH2AX foci is one of the earliest recognition step of DSB managed by the non-homologous end-joining (NHEJ), the major DSB repair pathway in humans[9]. During the DSB joining process, two ATM monomers reassociate on the DSB site and form the autophophorylated ATM (pATM) foci in nuclear, also visible by immunofluorescence. The RIANS model permits to predict radiosensitivity and radiosusceptibility with one of the highest statistical robustness.