Quantitative stakeholder-driven assessment of radiation protection issues via a PIANOFORTE online survey.

To enhance stakeholder engagement and foster the inclusion of interests of citizens in radiation protection research, a comprehensive online survey was developed within the framework of the European Partnership PIANOFORTE. This survey was performed in 2022 and presented an opportunity for a wide range of stakeholders to voice their opinions on research priorities in radiation protection for the foreseeable future. Simultaneously, it delved into pertinent issues surrounding general radiation protection. The PIANOFORTE e-survey was conducted in the English language, accommodating a diverse range of participants. Overall, 440 respondents provided their insights and feedback, representing a broad geographical reach encompassing 29 European countries, as well as Canada, China, Colombia, India, and the United States. To assess the outcomes, the Positive Matrix Factorization numerical model was applied, in addition to qualitative and quantitative assessment of individual responses, enabling the discernment of four distinct stakeholder groups with varying attitudes. While the questionnaire may not fully represent all stakeholders due to the limited respondent pool, it is noteworthy that approximately 70% of the participants were newcomers to comparable surveys, demonstrating a proactive attitude, a strong willingness to collaborate and the necessity to continuously engage with stakeholder groups. Among the individual respondents, distinct opinions emerged particularly regarding health effects of radiation exposure, medical use of radiation, radiation protection of workers and the public, as well as emergency and recovery preparedness and response. In cluster analysis, none of the identified groups had clear preferences concerning the prioritization of future radiation protection research topics.

The 2020 MELODI workshop on the effects of spatial and temporal variation in dose delivery.

A key activity of MELODI is to organise annual European meetings where scientific results and future directions and strategies of relevant research are discussed. The annual meetings, previously organised solely under the auspices of MELODI are, since 2016, jointly organised by the European platforms and referred to as European Radiation Protection Weeks (ERPW). In addition to ERPW meetings, MELODI organises and finances annual workshops dedicated to specific topics. Outputs and recommendations from the meetings are published as review articles. The 2020 workshop focussed on one of the cross cutting topics: the effects of spatial and temporal variation in dose delivery on disease risk. The current issue of REBS includes five review articles from the workshop on the effects of spatial and temporal variation in dose delivery and this editorial is a short summary of their content.

Heterogeneity of dose distribution in normal tissues in case of radiopharmaceutical therapy with alpha-emitting radionuclides.

Heterogeneity of dose distribution has been shown at different spatial scales in diagnostic nuclear medicine. In cancer treatment using new radiopharmaceuticals with alpha-particle emitters, it has shown an extensive degree of dose heterogeneity affecting both tumour control and toxicity of organs at risk. This review aims to provide an overview of generalized internal dosimetry in nuclear medicine and highlight the need of consideration of the dose heterogeneity within organs at risk. The current methods used for patient dosimetry in radiopharmaceutical therapy are summarized. Bio-distribution and dose heterogeneities of alpha-particle emitting pharmaceutical 223Ra (Xofigo) within bone tissues are presented as an example. In line with the strategical research agendas of the Multidisciplinary European Low Dose Initiative (MELODI) and the European Radiation Dosimetry Group (EURADOS), future research direction of pharmacokinetic modelling and dosimetry in patient radiopharmaceutical therapy are recommended.

Effects of spatial variation in dose delivery: what can we learn from radon-related lung cancer studies?

Exposure to radon progeny results in heterogeneous dose distributions in many different spatial scales. The aim of this review is to provide an overview on the state of the art in epidemiology, clinical observations, cell biology, dosimetry, and modelling related to radon exposure and its association with lung cancer, along with priorities for future research. Particular attention is paid on the effects of spatial variation in dose delivery within the organs, a factor not considered in radiation protection. It is concluded that a multidisciplinary approach is required to improve risk assessment and mechanistic understanding of carcinogenesis related to radon exposure. To achieve these goals, important steps would be to clarify whether radon can cause other diseases than lung cancer, and to investigate radon-related health risks in children or persons at young ages. Also, a better understanding of the combined effects of radon and smoking is needed, which can be achieved by integrating epidemiological, clinical, pathological, and molecular oncology data to obtain a radon-associated signature. While in vitro models derived from primary human bronchial epithelial cells can help to identify new and corroborate existing biomarkers, they also allow to study the effects of heterogeneous dose distributions including the effects of locally high doses. These novel approaches can provide valuable input and validation data for mathematical models for risk assessment. These models can be applied to quantitatively translate the knowledge obtained from radon exposure to other exposures resulting in heterogeneous dose distributions within an organ to support radiation protection in general.

Internal microdosimetry of alpha-emitting radionuclides.

At the tissue level, energy deposition in cells is determined by the microdistribution of alpha-emitting radionuclides in relation to sensitive target cells. Furthermore, the highly localized energy deposition of alpha particle tracks and the limited range of alpha particles in tissue produce a highly inhomogeneous energy deposition in traversed cell nuclei. Thus, energy deposition in cell nuclei in a given tissue is characterized by the probability of alpha particle hits and, in the case of a hit, by the energy deposited there. In classical microdosimetry, the randomness of energy deposition in cellular sites is described by a stochastic quantity, the specific energy, which approximates the macroscopic dose for a sufficiently large number of energy deposition events. Typical examples of the alpha-emitting radionuclides in internal microdosimetry are radon progeny and plutonium in the lungs, plutonium and americium in bones, and radium in targeted radionuclide therapy. Several microdosimetric approaches have been proposed to relate specific energy distributions to radiobiological effects, such as hit-related concepts, LET and track length-based models, effect-specific interpretations of specific energy distributions, such as the dual radiation action theory or the hit-size effectiveness function, and finally track structure models. Since microdosimetry characterizes only the initial step of energy deposition, microdosimetric concepts are most successful in exposure situations where biological effects are dominated by energy deposition, but not by subsequently operating biological mechanisms. Indeed, the simulation of the combined action of physical and biological factors may eventually require the application of track structure models at the nanometer scale.

The degree of inhomogeneity of the absorbed cell nucleus doses in the bronchial region of the human respiratory tract.

Inhalation of short-lived radon progeny is an important cause of lung cancer. To characterize the absorbed doses in the bronchial region of the airways due to inhaled radon progeny, mostly regional lung deposition models, like the Human Respiratory Tract Model (HRTM) of the International Commission on Radiological Protection, are used. However, in this model the site specificity of radiation burden in the airways due to deposition and fast airway clearance of radon progeny is not described. Therefore, in the present study, the Radact version of the stochastic lung model was used to quantify the cellular radiation dose distribution at airway generation level and to simulate the kinetics of the deposited radon progeny resulting from the moving mucus layer. All simulations were performed assuming an isotope ratio typical for an average dwelling, and breathing mode characteristic of a healthy adult sitting man. The study demonstrates that the cell nuclei receiving high doses are non-uniformly distributed within the bronchial airway generations. The results revealed that the maximum of the radiation burden is at the first few bronchial airway generations of the respiratory tract, where most of the lung carcinomas of former uranium miners were found. Based on the results of the present simulations, it can be stated that regional lung models may not be fully adequate to describe the radiation burden due to radon progeny. A more realistic and precise calculation of the absorbed doses from the decay of radon progeny to the lung requires deposition and clearance to be simulated by realistic models of airway generations.

Radon induced hyperplasia: effective adaptation reducing the local doses in the bronchial epithelium.

There is experimental and histological evidence that chronic irritation and cell death may cause hyperplasia in the exposed tissue. As the heterogeneous deposition of inhaled radon progeny results in high local doses at the peak of the bronchial bifurcations, it was proposed earlier that hyperplasia occurs in these deposition hot spots upon chronic radon exposure. The objective of the present study is to quantify how the induction of basal cell hyperplasia modulates the microdosimetric consequences of a given radon exposure. For this purpose, computational epithelium models were constructed with spherical cell nuclei of six different cell types based on histological data. Basal cell hyperplasia was modelled by epithelium models with additional basal cells and increased epithelium thickness. Microdosimetry for alpha-particles was performed by an own-developed Monte-Carlo code. Results show that the average tissue dose, and the average hit number and dose of basal cells decrease by the increase of the measure of hyperplasia. Hit and dose distribution reveal that the induction of hyperplasia may result in a basal cell pool which is shielded from alpha-radiation. It highlights that the exposure history affects the microdosimetric consequences of a present exposure, while the biological and health effects may also depend on previous exposures. The induction of hyperplasia can be considered as a radioadaptive response at the tissue level. Such an adaptation of the tissue challenges the validity of the application of the dose and dose rate effectiveness factor from a mechanistic point of view. As the location of radiosensitive target cells may change due to previous exposures, dosimetry models considering the tissue geometry characteristic of normal conditions may be inappropriate for dose estimation in case of protracted exposures. As internal exposures are frequently chronic, such changes in tissue geometry may be highly relevant for other incorporated radionuclides.

Heterogeneity of absorbed dose distribution in kidney tissues and dose-response modelling of nephrotoxicity in radiopharmaceutical therapy with beta-particle emitters: A review.

Absorbed dose heterogeneity in kidney tissues is an important issue in radiopharmaceutical therapy. The effect of absorbed dose heterogeneity in nephrotoxicity is, however, not fully understood yet, which hampers the implementation of treatment optimization by obscuring the interpretation of clinical response data and the selection of optimal treatment options. Although some dosimetry methods have been developed for kidney dosimetry to the level of microscopic renal substructures, the clinical assessment of the microscopic distribution of radiopharmaceuticals in kidney tissues currently remains a challenge. This restricts the anatomical resolution of clinical dosimetry, which hinders a thorough clinical investigation of the impact of absorbed dose heterogeneity. The potential of absorbed dose-response modelling to support individual treatment optimization in radiopharmaceutical therapy is recognized and gaining attraction. However, biophysical modelling is currently underexplored for the kidney, where particular modelling challenges arise from the convolution of a complex functional organization of renal tissues with the function-mediated dose distribution of radiopharmaceuticals. This article reviews and discusses the heterogeneity of absorbed dose distribution in kidney tissues and the absorbed dose-response modelling of nephrotoxicity in radiopharmaceutical therapy. The review focuses mainly on the peptide receptor radionuclide therapy with beta-particle emitting somatostatin analogues, for which the scientific literature reflects over two decades of clinical experience. Additionally, detailed research perspectives are proposed to address various identified challenges to progress in this field.

Datasets of in vitro clonogenic assays showing low dose hyper-radiosensitivity and induced radioresistance.

Low dose hyper-radiosensitivity and induced radioresistance are primarily observed in surviving fractions of cell populations exposed to ionizing radiation, plotted as the function of absorbed dose. Several biophysical models have been developed to quantitatively describe these phenomena. However, there is a lack of raw, openly available experimental data to support the development and validation of quantitative models. The aim of this study was to set up a database of experimental data from the public literature. Using Google Scholar search, 46 publications with 101 datasets on the dose-dependence of surviving fractions, with clear evidence of low dose hyper-radiosensitivity, were identified. Surviving fractions, their uncertainties, and the corresponding absorbed doses were digitized from graphs of the publications. The characteristics of the cell line and the irradiation were also recorded, along with the parameters of the linear-quadratic model and/or the induced repair model if they were provided. The database is available in STOREDB, and can be used for meta-analysis, for comparison with new experiments, and for development and validation of biophysical models.

Aerosol Transport Modeling: The Key Link Between Lung Infections of Individuals and Populations.

The recent COVID-19 pandemic has propelled the field of aerosol science to the forefront, particularly the central role of virus-laden respiratory droplets and aerosols. The pandemic has also highlighted the critical need, and value for, an information bridge between epidemiological models (that inform policymakers to develop public health responses) and within-host models (that inform the public and health care providers how individuals develop respiratory infections). Here, we review existing data and models of generation of respiratory droplets and aerosols, their exhalation and inhalation, and the fate of infectious droplet transport and deposition throughout the respiratory tract. We then articulate how aerosol transport modeling can serve as a bridge between and guide calibration of within-host and epidemiological models, forming a comprehensive tool to formulate and test hypotheses about respiratory tract exposure and infection within and between individuals.

Modeling of nursing care-associated airborne transmission of SARS-CoV-2 in a real-world hospital setting.

Respiratory transmission of SARS-CoV-2 from one older patient to another by airborne mechanisms in hospital and nursing home settings represents an important health challenge during the COVID-19 pandemic. However, the factors that influence the concentration of respiratory droplets and aerosols that potentially contribute to hospital- and nursing care-associated transmission of SARS-CoV-2 are not well understood. To assess the effect of health care professional (HCP) and patient activity on size and concentration of airborne particles, an optical particle counter was placed (for 24 h) in the head position of an empty bed in the hospital room of a patient admitted from the nursing home with confirmed COVID-19. The type and duration of the activity, as well as the number of HCPs providing patient care, were recorded. Concentration changes associated with specific activities were determined, and airway deposition modeling was performed using these data. Thirty-one activities were recorded, and six representative ones were selected for deposition modeling, including patient's activities (coughing, movements, etc.), diagnostic and therapeutic interventions (e.g., diagnostic tests and drug administration), as well as nursing patient care (e.g., bedding and hygiene). The increase in particle concentration of all sizes was sensitive to the type of activity. Increases in supermicron particle concentration were associated with the number of HCPs (r = 0.66; p < 0.05) and the duration of activity (r = 0.82; p < 0.05), while submicron particles increased with all activities, mainly during the daytime. Based on simulations, the number of particles deposited in unit time was the highest in the acinar region, while deposition density rate (number/cm2/min) was the highest in the upper airways. In conclusion, even short periods of HCP-patient interaction and minimal patient activity in a hospital room or nursing home bedroom may significantly increase the concentration of submicron particles mainly depositing in the acinar regions, while mainly nursing activities increase the concentration of supermicron particles depositing in larger airways of the adjacent bed patient. Our data emphasize the need for effective interventions to limit hospital- and nursing care-associated transmission of SARS-CoV-2 and other respiratory pathogens (including viral pathogens, such as rhinoviruses, respiratory syncytial virus, influenza virus, parainfluenza virus and adenoviruses, and bacterial and fungal pathogens).

From tangled banks to toxic bunnies; a reflection on the issues involved in developing an ecosystem approach for environmental radiation protection.

The objective of this paper is to present the results of discussions at a workshop held as part of the International Congress of Radiation Research (Environmental Health stream) in Manchester UK, 2019. The main objective of the workshop was to provide a platform for radioecologists to engage with radiobiologists to address major questions around developing an Ecosystem approach in radioecology and radiation protection of the environment. The aim was to establish a critical framework to guide research that would permit integration of a pan-ecosystem approach into radiation protection guidelines and regulation for the environment. The conclusions were that the interaction between radioecologists and radiobiologists is useful in particular in addressing field versus laboratory issues where there are issues and challenges in designing good field experiments and a need to cross validate field data against laboratory data and vice versa. Other main conclusions were that there is a need to appreciate wider issues in ecology to design good approaches for an ecosystems approach in radioecology and that with the capture of 'Big Data', novel tools such as machine learning can now be applied to help with the complex issues involved in developing an ecosystem approach.

Mutation induction by inhaled radon progeny modeled at the tissue level.

The observable responses of living systems to ionizing radiation depend on the level of biological organization studied. Understanding the relationships between the responses characteristic of the different levels of organization is of crucial importance. The main objective of the present study is to investigate how some cellular effects of radiation manifest at the tissue level by modeling mutation induction due to chronic exposure to inhaled radon progeny. For this purpose, a mathematical model of the bronchial epithelium was elaborated to quantify cell nucleus hits and cell doses. Mutagenesis was modeled considering endogenous as well as radiation-induced DNA damages and cell cycle shortening due to cell inactivation. The model parameters describing the cellular effects of radiation are obtained from experimental data. Cell nucleus hits, cell doses, and mutation induction were computed for the activity hot spots of the large bronchi at different exposures. Results demonstrate that the mutagenic effect of densely ionizing radiation is dominated by cell cycle shortening due to cell inactivation and not by DNA damages. This suggests that radiation burdens of non-progenitor cells play a significant role in mutagenesis in case of protracted exposures to densely ionizing radiation. Mutation rate as a function of dose rate exhibits a convex shape below a threshold. This threshold indicates the exhaustion of the tissue regeneration capacity of local progenitor cells. It is suggested that progenitor cell hyperplasia occurs beyond the threshold dose rate, giving a possible explanation of the inverse dose-rate effect observed in the epidemiology of lung cancer among uranium miners.

Effect of site-specific bronchial radon progeny deposition on the spatial and temporal distributions of cellular responses.

Inhaled short-lived radon progenies may deposit in bronchial airways and interact with the epithelium by the emission of alpha particles. Simulation of the related radiobiological effects requires the knowledge of space and time distributions of alpha particle hits and biological endpoints. Present modelling efforts include simulation of radioaerosol deposition patterns in a central bronchial airway bifurcation, modelling of human bronchial epithelium, generation of alpha particle tracks, and computation of spatio-temporal distributions of cell nucleus hits, cell killing and cell transformation events. Simulation results indicate that the preferential radionuclide deposition at carinal ridges plays an important role in the space and time evolution of the biological events. While multiple hits are generally rare for low cumulative exposures, their probability may be quite high at the carinal ridges of the airway bifurcations. Likewise, cell killing and transformation events also occur with higher probability in this area. In the case of uniform surface activities, successive hits as well as cell killing and transformation events within a restricted area (say 0.5 mm(2)) are well separated in time. However, in the case of realistic inhomogeneous deposition, they occur more frequently within the mean cycle time of cells located at the carinal ridge even at low cumulative doses. The site-specificity of radionuclide deposition impacts not only on direct, but also on non-targeted radiobiological effects due to intercellular communication. Incorporation of present results into mechanistic models of carcinogenesis may provide useful information concerning the dose-effect relationship in the low-dose range.

DNA repair inhibitors sensitize cells differently to high and low LET radiation.

The aim of this study was to investigate effects of high LET α-radiation in combination with inhibitors of DDR (DNA-PK and ATM) and to compare the effect with the radiosensitizing effect of low LET X-ray radiation. The various cell lines were irradiated with α-radiation and with X-ray. Clonogenic survival, the formation of micronuclei and cell cycle distribution were studied after combining of radiation with DDR inhibitors. The inhibitors sensitized different cancer cell lines to radiation. DNA-PKi affected survival rates in combination with α-radiation in selected cell lines. The sensitization enhancement ratios were in the range of 1.6-1.85 in cancer cells. ATMi sensitized H460 cells and significantly increased the micronucleus frequency for both radiation qualities. ATMi in combination with α-radiation reduced survival of HEK293. A significantly elicited cell cycle arrest in G2/M phase after co-treatment of ATMi with α-radiation and X-ray. The most prominent treatment effect was observed in the HEK293 by combining α-radiation and inhibitions. ATMi preferentially sensitized cancer cells and normal HEK293 cells to α-radiation. DNA-PKi and ATMi can sensitize cancer cells to X-ray, but the effectiveness was dependent on cancer cells itself. α-radiation reduced proliferation in primary fibroblast without G2/M arrest.

Deposition distribution of the new coronavirus (SARS-CoV-2) in the human airways upon exposure to cough-generated droplets and aerosol particles.

The new coronavirus disease 2019 (COVID-19) has been emerged as a rapidly spreading pandemic. The disease is thought to spread mainly from person-to-person through respiratory droplets produced when an infected person coughs, sneezes, or talks. The pathogen of COVID-19 is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It infects the cells binding to the angiotensin-converting enzyme 2 receptor (ACE2) which is expressed by cells throughout the airways as targets for cellular entry. Although the majority of persons infected with SARS-CoV-2 experience symptoms of mild upper respiratory tract infection, in some people infections of the acinar airways result in severe, potentially fatal pneumonia. However, the induction of COVID-19 pneumonia requires that SARS-CoV-2 reaches the acinar airways. While huge efforts have been made to understand the spread of the disease as well as the pathogenesis following cellular entry, much less attention is paid to how SARS-CoV-2 from the environment reach the receptors of the target cells. The aim of the present study is to characterize the deposition distribution of SARS-CoV-2 in the airways upon exposure to cough-generated droplets and aerosol particles. For this purpose, the Stochastic Lung Deposition Model has been applied. Particle size distribution, breathing parameters supposing normal breathing through the nose, and viral loads were taken from the literature. We found that the probability of direct infection of the acinar airways due to inhalation of particles emitted by a bystander cough is very low. As the number of viruses deposited in the extrathoracic airways is about 7 times higher than in the acinar airways, we concluded that in most cases COVID-19 pneumonia must be preceded by SARS-CoV-2 infection of the upper airways. Our results suggest that without the enhancement of viral load in the upper airways, COVID-19 would be much less dangerous. The period between the onset of initial symptoms and the potential clinical deterioration could provide an opportunity for prevention of pneumonia by blocking or significantly reducing the transport of viruses towards the acinar airways. Therefore, even non-specific treatment forms like disinfection of the throat and nasal and oral mucosa may effectively keep the viral load of the upper airways low enough to avoid or prolong the progression of the disease. In addition, using a tissue or cloth in order to absorb droplets and aerosol particles emitted by own coughs of infected patients before re-inhalation is highly recommended even if they are alone in quarantine.

SURVEY ON DATA MANAGEMENT IN RADIATION PROTECTION RESEARCH.

The importance of datasharing is of increasing concern to funding bodies and institutions. With some prescience, the radiobiology community has established datasharing infrastructures over the last two decades, including STORE; however, the utilization of these databases is disappointing. The aim of the present study was to identify the current state of datasharing amongst researchers in radiation protection, and to identify barriers to effective sharing. An electronic survey was prepared, including questions on post-publication data provision, institutional, funding agency, and journal policies, awareness of datasharing infrastructures, attitudinal barriers and technical support. The survey was sent to the members of a mailing list maintained by the EC funded CONCERT project. Responses identified that the radiation protection community shared similar concerns to other groups canvassed in earlier studies; the perceived negative impact of datasharing on competitiveness, career development and reputation, along with concern about the costs of data management. More surprising was the lack of awareness of existing datasharing platforms. We find that there is a clear need for education and training in data management and for a significant programme of improving awareness of Open Data issues.

COMPUTATIONAL MODELING OF LOW DOSE HYPER-RADIOSENSITIVITY AND INDUCED RADIORESISTANCE APPLYING THE PRINCIPLE OF MINIMUM MUTATION LOAD.

Low dose hyper-radiosensitivity (HRS) and induced radioresistance (IRR) can be observed in the dose dependence of survival of many different cell lines. While surviving fraction decreases exponentially in a large-scale view, a local minimum can be found at around 0.5 Gy. Although, there is evidence that the regulation of apoptosis and DNA repair are involved in HRS and IRR, the fundamental causes of the phenomena remain unclear. The objective of the present study is to test whether the principle of minimum mutation load can provide an explanation for both low dose HRS and IRR. For this purpose, a mathematical model was elaborated considering radiation induced mutagenic DNA lesions as well as cell divisions as sources of mutations. It was presumed that cell number is in dynamic equilibrium in the tissue, the number of mutations follows Poisson distribution, and its average is proportional to absorbed dose. For each value of absorbed dose, the minimum number of mutations were computed for different surviving fractions. Then that surviving fraction was plotted that results in the lowest number of mutations. One minimum or multiple minima can be seen in the dose dependence of surviving fractions with reasonable values for the model parameters: spontaneous and radiation induced mutation rate. Although the mechanisms remain unclear, the principle of minimum mutation load provides a potential explanation for low dose HRS and IRR and for the fact that they are mostly observed in cell lines with defected DNA repair.

QUANTITATIVE ANALYSIS OF THE POTENTIAL ROLE OF BASAL CELL HYPERPLASIA IN THE RELATIONSHIP BETWEEN CLONAL EXPANSION AND RADON CONCENTRATION.

Applying the two-stage clonal expansion model to epidemiology of lung cancer among uranium miners, it has been revealed that radon acts as a promoting agent facilitating the clonal expansion of already mutated cells. Clonal expansion rate increases non-linearly by radon concentration showing a plateau above a given exposure rate. The underlying mechanisms remain unclear. Earlier we proposed that progenitor cell hyperplasia may be induced upon chronic radon exposure. The objective of the present study is to test whether the induction of hyperplasia may provide a quantitative explanation for the plateau in clonal expansion rate. For this purpose, computational epithelium models were prepared with different number of basal cells. Cell nucleus hits were computed by an own-developed Monte-Carlo code. Surviving fractions were estimated based on the number of cell nucleus hits. Cell division rate was computed supposing equilibrium between cell death and cell division. It was also supposed that clonal expansion rate is proportional to cell division rate, and therefore the relative increase in cell division rate and clonal expansion rate are the same functions of exposure rate. While the simulation results highly depend on model parameters with high uncertainty, a parameter set has been found resulting in a cell division rate-exposure rate relationship corresponding to the plateau in clonal expansion rate. Due to the high uncertainty of the applied parameters, however, further studies are required to decide whether the induction of hyperplasia is responsible for the non-linear increase in clonal expansion rate or not. Nevertheless, the present study exemplifies how computational modelling can contribute to the integration of observational and experimental radiation protection research.