Biological dosimetry. Development, potential and possible applications at national and international level

Biological dosimetry is an internationally recognized method which enables the quantification of individually received radiation doses based on biological indicators in the event of unclear exposure to ionizing radiation in humans. For this purpose, radiation-related changes on the chromosomal level are analyzed in lymphocytes of the peripheral blood. These changes can be assigned to a radiation dose on the basis of a pronounced dose-effect relationship. Among the various biological markers for ionizing radiation, the analysis of dicentric chromosomes is the "gold standard" of biological dosimetry. Dicentric chromosomes have long been known as biomarkers for ionizing radiation. In recent years, the method has evolved considerably due to new technical advances, so that software-based, automated analysis methods are now available in addition to conventional manual evaluation. The dissertation shows new results that have been achieved in various EU research projects and illustrates the qualitative and quantitative optimization of biological dosimetry, especially the analysis of dicentric chromosomes, for use in radiation protection as well as in radiation biological research. The regular performance of quality-assured proficiency tests has proven to be an essential instrument for achieving comparable results on an international level. MULTIBIODOSE (FP 7 - 241536) used various strategies to adapt the dicentric chromosome analysis to a major radiation accident, thereby increasing the throughput of the method and accelerating the availability of dose estimates. In addition to the manual evaluation in "triage" mode, i.e. the number of evaluated cells is greatly reduced, the web-based evaluation of electronic images of metaphases on the screen was used as a digital medium and the potential of automated scoring of dicentric chromosomes was tested as a new way to quickly identify radiation exposed individuals who need medical care. Overall, the results showed a very good correlation between the 8 participating laboratories, which was attributed to the fact that mainly laboratories with many years of experience in the field of biological dosimetry were involved. For all tested radiation scenarios (acute, protracted and partial body radiation) the radiation doses > 1 Gy could be clearly distinguished from the unirradiated control samples. The strong limitation of the evaluated cells to save time caused difficulties with the protracted irradiation of high doses and with partial body exposure to low doses in almost all evaluation strategies. In these cases, the subsequent analyzes of additional cells is indicated in order to rule out false negative results. The goal of establishing a sustainable network for biological and retrospective dosimetry in Europe was pursued within the framework of RENEB (FP 7 - 295513). 23 institutions from 16 EU countries participated in increasing the capacity of the method in the event of a major radiation accident. In order to ensure the comparability of the results from the various laboratories, it was necessary to carry out quality-assured inter-laboratory exercises. These were based on each other in terms of content and scope and were initially carried out only internally within RENEB and then at a global level. Training courses and scientific exchange between the laboratories enabled improvements of the implementation, including transport and delivery as well as the dose estimation, especially in the higher dose range. The potential of dicentric chromosome analysis for use in the context of a major radiation accident could be clarified. The use of the semi-automatic evaluation of dicentric chromosomes for radiation biological research provided an important contribution to show differences in agedependent radiation sensitivity at low doses (<100 mSv) and, thus, the need for further research in this area. The method was used for examining the radiation sensitivity of different age groups in the dose range relevant for diagnostic CT images (41 mSv). Significantly more induced chromosome damage was detected in the blood lymphocytes in children <5 years than in adults. The latter could only be shown by increasing the statistical power, which was achieved by strongly increasing the number of cells. Thanks to the semi-automated evaluation process, the results could be obtained much faster compared to conventional evaluation, which also opens up new application possibilities for the automated evaluation of dicentric chromosomes.