Understanding the biological mechanisms involved in the response to exposure to ionizing radiation is very important. This work package aims to test different biological markers of exposure and also of sensitivity to identify mechanisms behind the low dose hypersensitivity observed in paediatric patients exposed to x-rays from CT. On the one hand this may be used for improving radiation protection strategies in situations where exposure to radiation is unavoidable (e.g. medical radiation). On the other, biomarkers are sought to identify radiation sensitive subjects who should not be exposed to certain doses. Within the EPI-CT project, some fundamental research on testing biological mechanisms and biomarkers will be performed as well feasibility studies, investigating the benefit of further research.
Chromosomal aberrations may be used to evaluate the radiation-induced cancer risks as they are on the biological pathway to cancer development. From three different age groups, ranging from newborns to adolescents, blood samples will be taken and irradiated by a common CT scanner. Possibly observed differences in aberrations by age groups may indicate an age dependent radiosensitivity. The results will be used to access the feasibility of conducting a larger study including more blood donors.
Another approach concentrates on monitoring DNA-damage by accessing DNA double strand breaks (DSB). From a random group of paediatric patients blood samples will be taken before and after the CT examination. These samples will be sent to different laboratories all analysing the amount of DSBs. The frequencies will be compared in-between the laboratories and with the results from adolescent donors, whose blood was irradiated to lower doses of ionizing radiation.
It has been shown in other studies that biochemical composition of urine has been different in persons having adverse effects after radiotherapy from people who did not. By this way, biomarkers of radiosensitivity could be also identified. This approach will assess the feasibility of using less invasive biological samples (e.g. saliva and urine instead of blood), as the collection of the latter is more complicated. Subsequent analyses will determine if saliva can replace serum as a biosample in which biomarkers of radiation-induced stress response can be determined.
Evaluating gene expressions before and after CT exposure make it possible to detect early radiation-induced biological markers and will enhance the understanding of biological mechanisms related to radiosensitivity. Gene expression analysis therefore will be performed on the blood samples taken from the sample mentioned above and on blood samples irradiated with different doses in an experimental setting.
Cytokines are expected to be important for the cell-cell communication: different types tend to be expressed at different times. Again blood samples will be taken before and after exposure to CTs. Parts of these samples will additionally irradiated in an experimental setting. Comprehensive analyses of the released cytokines in respect of time and absorbed dose will help to understand the inbound biochemical dynamics.