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The goal of this study was to retrospectively estimate the exposure dose of a victim from the Lilo radiological accident in Georgia after 22 y and compare it with the original cytogenetics-based analysis performed in our laboratory. Similar types of studies have been published, notably involving victims of the Chernobyl, Goiânia and Tammiku accidents. Nevertheless, their estimations were done after shorter periods of time post-exposure, and in some cases, the exposure might not have been exclusively of an external nature. In this study, Fluorescence In Situ Hybridization (FISH) was used to score chromosomal translocations in lymphocytes from a recent blood sample of the victim and the dose assessment was performed using our laboratory's FISH calibration curve. The resulting whole-body exposure dose of 0.35 Gy [0.12, 0.72] was similar to the one obtained when reanalysing the original scoring data from 1997 (0.38 Gy [0.13–0.75]), suggesting that our current calibration curve could be used for relative dose estimations long time after external exposure. [ABSTRACT FROM AUTHOR]

After large-scale radiation accidents where many individuals are suspected to be exposed to ionizing radiation, biological and physical retrospective dosimetry assays are important tools to aid clinical decision making by categorizing individuals into unexposed/minimally, moderately or highly exposed groups. Quality-controlled inter-laboratory comparisons of simulated accident scenarios are regularly performed in the frame of the European legal association RENEB (Running the European Network of Biological and Physical retrospective Dosimetry) to optimize international networking and emergency readiness in case of large-scale radiation events. In total 33 laboratories from 22 countries around the world participated in the current RENEB inter-laboratory comparison 2021 for the dicentric chromosome assay. Blood was irradiated in vitro with X rays (240 kVp, 13 mA, ∼75 keV, 1 Gy/min) to simulate an acute, homogeneous whole-body exposure. Three blood samples (no. 1: 0 Gy, no. 2: 1.2 Gy, no. 3: 3.5 Gy) were sent to each participant and the task was to culture samples, to prepare slides and to assess radiation doses based on the observed dicentric yields from 50 manually or 150 semi-automatically scored metaphases (triage mode scoring). Approximately two-thirds of the participants applied calibration curves from irradiations with γ rays and about 1/3 from irradiations with X rays with varying energies. The categorization of the samples in clinically relevant groups corresponding to individuals that were unexposed/minimally (0–1 Gy), moderately (1–2 Gy) or highly exposed (>2 Gy) was successfully performed by all participants for sample no. 1 and no. 3 and by ≥74% for sample no. 2. However, while most participants estimated a dose of exactly 0 Gy for the sham-irradiated sample, the precise dose estimates of the samples irradiated with doses >0 Gy were systematically higher than the corresponding reference doses and showed a median deviation of 0.5 Gy (sample no. 2) and 0.95 Gy (sample no. 3) for manual scoring. By converting doses estimated based on γ-ray calibration curves to X-ray doses of a comparable mean photon energy as used in this exercise, the median deviation decreased to 0.27 Gy (sample no. 2) and 0.6 Gy (sample no. 3). The main aim of biological dosimetry in the case of a large-scale event is the categorization of individuals into clinically relevant groups, to aid clinical decision making. This task was successfully performed by all participants for the 0 Gy and 3.5 Gy samples and by 74% (manual scoring) and 80% (semiautomatic scoring) for the 1.2 Gy sample. Due to the accuracy of the dicentric chromosome assay and the high number of participating laboratories, a systematic shift of the dose estimates could be revealed. Differences in radiation quality (X ray vs. γ ray) between the test samples and the applied dose effect curves can partly explain the systematic shift. There might be several additional reasons for the observed bias (e.g., donor effects, transport, experimental conditions or the irradiation setup) and the analysis of these reasons provides great opportunities for future research. The participation of laboratories from countries around the world gave the opportunity to compare the results on an international level. [ABSTRACT FROM AUTHOR]

Purpose: In this work, we present simulated double‐strand breaks (DSBs) obtained for two human cell nucleus geometries. The first cell nucleus represents fibroblasts, filled with DNA molecules in different compaction forms: heterochromatin or euchromatin only. The second one represents an endothelial cell nucleus, either filled with heterochromatin only or with a uniform distribution of 48% of heterochromatin and 52% of euchromatin, obtained from measurements carried out at IRSN. Protons and alpha particles of different energies were used as projectiles. Each cell nucleus model includes a multi‐scale description of the DNA target from the molecular level to the whole human genome representation. Methods: The cell nucleus models were generated using an extended version of the DnaFabric software in which a new model of euchromatin was implemented in addition to the existing model of heterochromatin. Thus, each nucleus model contains the complete human genome (a total of 6 Gbp) in the G0/G1 phase of the cycle, filled with a continuous chromatin fiber per chromosome that can take into account the heterochromatin and the euchromatin compaction. These geometries were then exported to a simulation chain using the Monte Carlo toolkit Geant4‐DNA to perform computations of the physical, physicochemical, and chemical stages, in order to evaluate the influence of chromatin compaction on DSB induction and the contribution of direct and indirect damage, as well as DSB complexity. Results: More direct damage and less indirect damage were observed in the heterochromatin than in the euchromatin. Nevertheless, no difference in terms of DSB complexity was observed between those formed in the heterochromatin or the euchromatin models. Yields of DSB/Gy/Gbp show an increase when both heterochromatin and euchromatin models are taken into account, compared to when only heterochromatin is considered. Conclusions: The results presented indicate that the chromatin compaction decreases DNA damage generated by ionizing radiation and thus, DNA compaction should be considered for the simulation of DNA repair and other cellular outcomes. [ABSTRACT FROM AUTHOR]

Proton and ion beams are radiotherapy modalities of increasing importance and interest. Because of the different biological dose response of these radiations as compared with high-energy photon beams, the current approach of treatment prescription is based on the product of the absorbed dose to water and a biological weighting factor, but this is found to be insufficient for providing a generic method to quantify the biological outcome of radiation. It is therefore suggested to define new dosimetric quantities that allow a transparent separation of the physical processes from the biological ones. Given the complexity of the initiation and occurrence of biological processes on various time and length scales, and given that neither microdosimetry nor nanodosimetry on their own can fully describe the biological effects as a function of the distribution of energy deposition or ionization, a multiscale approach is needed to lay the foundation for the aforementioned new physical quantities relating track structure to relative biological effectiveness in proton and ion beam therapy. This article reviews the state-of-the-art microdosimetry, nanodosimetry, track structure simulations, quantification of reactive species, reference radiobiological data, cross-section data and multiscale models of biological response in the context of realizing the new quantities. It also introduces the European metrology project, Biologically Weighted Quantities in Radiotherapy, which aims to investigate the feasibility of establishing a multiscale model as the basis of the new quantities. A tentative generic expression of how the weighting of physical quantities at different length scales could be carried out is presented. [ABSTRACT FROM AUTHOR]

The purpose of this work is to evaluate the influence of the chromatin condensation on the number of direct double-strand break (DSB) damages induced by ions. Two geometries of chromosome territories containing either condensed or decondensed chromatin were implemented as biological targets in the Geant4 Monte Carlo simulation code and proton and alpha irradiation was simulated using the Geant4-DNA processes. A DBSCAN algorithm was used in order to detect energy deposition clusters that could give rise to single-strand breaks or DSBs on the DNA molecule. The results of this study show an increase in the number and complexity of DNA DSBs in condensed chromatin when compared with decondensed chromatin. [ABSTRACT FROM AUTHOR]

Relative Biological Effectiveness (RBE) values are used to characterise the biological efficiency of different radiation qualities relative to photon irradiations. The RBE–high linear energy transfer (LET) relation for ion irradiations presents general features that the authors propose to look at using a nanometric description of the energy deposition of these ion irradiations (protons and alphas of different energies). In this work, the simulation of the energy transfer points in the tracks was made by Monte Carlo method using the Geant4-DNA processes and a nanometric description of the target of interest for studying biological effects, the DNA molecule. Results were obtained concerning the sensitive volume to be considered for direct DNA clustered damages that could be related to late biological effects. [ABSTRACT FROM AUTHOR]

In 2011, a serious radiation accident occurred in Stamboliyski, Bulgaria, in an industrial sterilisation facility using very-high-activity 60Co sources. For the five persons accidentally exposed, biological dosimetry based on dicentric analysis was performed in Sofia and in Paris, where the patients were transferred for treatment. Before completing the chromosomal dose assessment, and for the most exposed person, a preliminary cytogenetic evaluation based on electronically transmitted metaphase images was made. The averaged acute whole-body dose estimates for the five patients ranged from 5.2 to 1.2 Gy, and good agreement was obtained between the two laboratories. The patients were also assessed by their prodromal responses and depressed blood cell counts over the first week. The cytogenetic dose estimates were in good accord with those derived from the blood counts, and both techniques indicated that, for the two most seriously exposed persons both techniques indicated that the initial prodromal reactions had suggested somewhat less severe exposure. [ABSTRACT FROM PUBLISHER]

Fundamentals of biological dosimetry are described in the International Atomic Energy Agency manual, but all over the world each laboratory is using its own protocol. To test the influence of protocol variations, some blood samples were exposed to 0.5 Gy of gamma radiation and mitotic index and dicentric rates were measured under different experimental conditions. The effect of seven parameters [bromodeoxyuridin (BrdU), phytohaemagglutinin and colcemid concentrations, blood and medium volumes, culture duration and incubation temperature] was tested using a Placket and Burman experimental design. The analysis reveals that the mitotic index was influenced by the concentration of BrdU, medium and blood volumes, the culture duration and the temperature. However, none of the factors has a significant impact on the yield of dicentrics. The dicentric assay is robust against reagent variations within the range tested. These results could be used by relevant laboratories as elements of their procedures robustness in any event requiring such demonstration. [ABSTRACT FROM AUTHOR]

The current focus on networking and mutual assistance in the management of radiation accidents or incidents has demonstrated the importance of a joined-up approach in physical and biological dosimetry. To this end, the European Radiation Dosimetry Working Group 10 on ‘Retrospective Dosimetry’ has been set up by individuals from a wide range of disciplines across Europe. Here, established and emerging dosimetry methods are reviewed, which can be used immediately and retrospectively following external ionising radiation exposure. Endpoints and assays include dicentrics, translocations, premature chromosome condensation, micronuclei, somatic mutations, gene expression, electron paramagnetic resonance, thermoluminescence, optically stimulated luminescence, neutron activation, haematology, protein biomarkers and analytical dose reconstruction. Individual characteristics of these techniques, their limitations and potential for further development are reviewed, and their usefulness in specific exposure scenarios is discussed. Whilst no single technique fulfils the criteria of an ideal dosemeter, an integrated approach using multiple techniques tailored to the exposure scenario can cover most requirements. [ABSTRACT FROM PUBLISHER]

The purpose of this study was to evaluate the in vivo dose-response relation of chromosome aberration formation and distribution in a context of localised and fractionated radiotherapy. Cytogenetic analysis was applied to eight patients, all treated for the same tumour localisation; the same localisation was used to prevent the variability usually observed between patients treated with radiotherapy and to allow the corresponding roles of the size of irradiation field and of the dose rate to be studied. The yield of dicentrics, centric rings and fragments was measured in blood samples taken before treatment, during the course of radiotherapy and up to 6 months after. After the first fraction of radiotherapy, we observed that the whole-body dose estimated from the yield of dicentrics and rings was higher (0.35±0.2 Gy) than the calculated equivalent whole-body dose (0.07±0.04 Gy). By contrast, the partial-body dose derived from the Qdr (quotient of dicentrics and rings) model was estimated to be 2.2±0.3 Gy, which agreed quite well with the dose delivered to the tumour (2.1±0.1 Gy). We also found a correlation between the yield of induced chromosome aberrations and the target field size (p=0.014). U-value analysis showed that the distribution of dicentrics and rings was overdispersed, despite the fractionation of the exposure, and a positive correlation between the U-value and the dose rate was observed (p=0.017). Overall, these results suggest that the proportion of undamaged lymphocytes could increase with the dose rate. [ABSTRACT FROM AUTHOR]

In this work we present results obtained in the frame of the BioQuaRT project. The objective of the study was the correlation between the number of radiation-induced double strand breaks (DSB) of the DNA molecule and the probability of detecting nuclear foci after targeted microbeam irradiation of cells with protons and alpha particles of different LET. The former were obtained by simulation with new methods integrated into Geant4-DNA that permit calculating the number of DSB in a DNA target model induced by direct and indirect radiation effects. A particular focus was laid in this work on evaluating the influence of different criteria applied to the simulated results for predicting the formation of a direct SSB. Indeed, these criteria have an important impact on the predicted number of DSB per particle track and its dependence with LET. Among the criteria tested in this work, the case that a direct radiation interaction leads to a strand break if the cumulative energy deposited in the backbone part of one nucleotide exceeds a threshold of 17.5 eV leads to the best agreement with the relative LET dependence of number of radiation induced foci. Further calculations and experimental data are nevertheless needed in order to fix the simulation parameters and to help interpreting the biological experimental data observed by immunofluorescence in terms of the DSB complexity.