Does the number of irradiated cells influence the spatial distribution of bystander effects?

There is growing evidence that the radiation effects at low doses are not adequately described by a simple linear extrapolation from high doses, due, among others, to bystander effects. Though several studies have been published on this topic, the explanation of the mechanisms describing the bystander effects remains unclear. This study aims at understanding how the bystander signals are or can be propagated in the cell culture, namely if the number of irradiated cells influences the bystander response. An A549 cell line was exposed to several doses of α-particles, being the bystander response quantified in two non-irradiated areas. The radius of irradiated areas differs by a factor of 2, and the non-irradiated areas were optimally designed to have the same number of cells. Our results show evidence for bystander effects occurring in cells far away from the irradiated ones, meaning that bystander signals can easily spread throughout the cell culture. Additionally, our study highlights that the damage caused by radiation on the surrounding of irradiated areas could be different according to the number of irradiated cells, i.e., for the same dose value; the overall cellular damage could be different.

EURADOS coordinated action on research, quality assurance and training of internal dose assessments.

EURADOS working group on 'Internal Dosimetry (WG7)' represents a frame to develop activities in the field of internal exposures as coordinated actions on quality assurance (QA), research and training. The main tasks to carry out are the update of the IDEAS Guidelines as a reference document for the internal dosimetry community, the implementation and QA of new ICRP biokinetic models, the assessment of uncertainties related to internal dosimetry models and their application, the development of physiology-based models for biokinetics of radionuclides, stable isotope studies, biokinetic modelling of diethylene triamine pentaacetic acid decorporation therapy and Monte-Carlo applications to in vivo assessment of intakes. The working group is entirely supported by EURADOS; links are established with institutions such as IAEA, US Transuranium and Uranium Registries (USA) and CEA (France) for joint collaboration actions.

Cellular burdens and biological effects on tissue level caused by inhaled radon progenies.

In the case of radon exposure, the spatial distribution of deposited radioactive particles is highly inhomogeneous in the central airways. The object of this research is to investigate the consequences of this heterogeneity regarding cellular burdens in the bronchial epithelium and to study the possible biological effects at tissue level. Applying computational fluid and particle dynamics techniques, the deposition distribution of inhaled radon daughters has been determined in a bronchial airway model for 23 min of work in the New Mexico uranium mine corresponding to 0.0129 WLM exposure. A numerical epithelium model based on experimental data has been utilised in order to quantify cellular hits and doses. Finally, a carcinogenesis model considering cell death-induced cell-cycle shortening has been applied to assess the biological responses. Present computations reveal that cellular dose may reach 1.5 Gy, which is several orders of magnitude higher than tissue dose. The results are in agreement with the histological finding that the uneven deposition distribution of radon progenies may lead to inhomogeneous spatial distribution of tumours in the bronchial airways. In addition, at the macroscopic level, the relationship between cancer risk and radiation burden seems to be non-linear.

Internal dosimetry: towards harmonisation and coordination of research.

The CONRAD Project is a Coordinated Network for Radiation Dosimetry funded by the European Commission 6th Framework Programme. The activities developed within CONRAD Work Package 5 ('Coordination of Research on Internal Dosimetry') have contributed to improve the harmonisation and reliability in the assessment of internal doses. The tasks carried out included a study of uncertainties and the refinement of the IDEAS Guidelines associated with the evaluation of doses after intakes of radionuclides. The implementation and quality assurance of new biokinetic models for dose assessment and the first attempt to develop a generic dosimetric model for DTPA therapy are important WP5 achievements. Applications of voxel phantoms and Monte Carlo simulations for the assessment of intakes from in vivo measurements were also considered. A Nuclear Emergency Monitoring Network (EUREMON) has been established for the interpretation of monitoring data after accidental or deliberate releases of radionuclides. Finally, WP5 group has worked on the update of the existing IDEAS bibliographic, internal contamination and case evaluation databases. A summary of CONRAD WP5 objectives and results is presented here.

Coordination of research on internal dosimetry in Europe: the CONRAD project.

The EUropean RAdiation DOSimetry Group (EURADOS) initiated in 2005 the CONRAD Project, a Coordinated Network for Radiation Dosimetry funded by the European Commission (EC), within the 6th Framework Programme (FP). The main purpose of CONRAD is to generate a European Network in the field of Radiation Dosimetry and to promote both research activities and dissemination of knowledge. The objective of CONRAD Work Package 5 (WP5) is the coordination of research on assessment and evaluation of internal exposures. Nineteen institutes from 14 countries participate in this action. Some of the activities to be developed are continuations of former European projects supported by the EC in the 5th FP (OMINEX and IDEAS). Other tasks are linked with ICRP activities, and there are new actions never considered before. A collaboration is established with CONRAD Work Package 4, dealing with Computational Dosimetry, to organise an intercomparison on Monte Carlo modelling for in vivo measurements of (241)Am deposited in a knee phantom. Preliminary results associated with CONRAD WP5 tasks are presented here.

[Investigating the possibility of aerosol therapy individualization using the stochastic lung model]. / Investigarea posibilitatii de a individualiza terapia cu aerosoli cu ajutorul modelului pulmonar stochastic.

The aim of our study is to examine the possibility of individualizing aerosol therapy, by determining the ideal diameter of the inhaled particles and the optimal breathing pattern, using a computerized simulation program. In order to find the optimal breathing pattern, we used different variations of the tidal volume and breathing period. We tried to determine the ideal particle diameter by carrying out a series of simulations for particles with diameters ranging from 1 to 10 microns. Our results show that increasing the particle diameter will lead to higher deposition values in the upper respiratory regions and bronchi, and smaller values in the acinary regions of the lung. Repeated simulations have led to two different ideal particle diameters, according to the localization of the desired effect. This way, for the bronchial regions the ideal particle diameter is 10 microns, and for the acinary regions 2 microns.

Detailed mathematical description of the geometry of airway bifurcations.

Health effects related to the deposition of inhaled aerosol particles in the respiratory system strongly depend on the local deposition patterns. These patterns are highly sensitive to the shape of the airway geometry. The current study presents an exact mathematical description of a morphologically realistic airway bifurcation by further developing an earlier study of the published literature. In addition, numerical methods are elaborated to solve some important tasks, which are necessary for the development of computational fluid dynamics (CFD) techniques in the area of aerosol deposition calculations in the airways. Finally, single and multiple airway geometries and computational grids are generated and analysed.

Simulation of deposition and clearance of inhaled particles in central human airways.

In this study local distributions of deposited inhaled particles such as radon progenies in realistic human airway bifurcation models of bronchial generations one to six are computed for different geometries, inlet flow profiles, flow rates and particle sizes with computational fluid particle dynamics methods. The movement of the mucus layer in the large central human airways is also simulated by computational fluid dynamic techniques. There is experimental evidence that bronchogenic carcinomas mainly originate at the central zone of the large airway bifurcations, where primary hot-spots of deposition have been found. However, current lung deposition models do not take into consideration the inhomogeneity of deposition within the airways. The inhomogeneous movement of the mucus layer may strongly influence the effect of primary deposition. On the basis of our results, both the deposition and the clearance patterns are highly non-uniform, especially in the vicinity of the carinal ridge of the bifurcations.

Etched track detectors and the low dose problem.

The risk to human health of exposure to low-level radiation is not precisely known yet. One way of studying this is to carry out in vitro biological experiments with cell cultures and to extend the conclusions to biological models. To relate the macroscopically deteminable 'low dose' to the damage of cells caused by a certain type of ionising particle is nearly impossible. therefore the number of hits and the imparted energy are the significant quantities. They can be estimated by particle transport calculations and by direct measurements. The effect of low dose was investigated in radio-adaptation experiments when mono-layers of different unsynchronised cell cultures were irradiated by neutrons produced in the filtered beam of the Budapest Research Reactor (BRR). The energy deposition was investigated by replacing the mono-layers with etched track detectors of the CR-39 type.

In vitro cell irradiation systems based on 210Po alpha source: construction and characterisation.

One way of studying the risk to human health of low-level radiation exposure is to make biological experiments on living cell cultures. Two 210Po alpha-particle emitting devices, with 0.5 and 100 MBq activity, were designed and constructed to perform such experiments irradiating monolayers of cells. Estimates of dose rate at the cell surface were obtained from measurements by a PIPS alpha-particle spectrometer and from calculations by the SRIM 2000, Monte Carlo charged particle transport code. Particle fluence area distributions were measured by solid state nuclear track detectors. The design and dosimetric characterisation of the devices are discussed.

Modelling carcinogenic effects of low doses of inhaled radon progenies.

In this study, cellular hit probabilities of alpha particles emitted by inhaled radon progenies in sensitive epithelial cell nuclei were simulated at low exposure levels to obtain useful data for the rejection or in support of the linear no-threshold dose-effect hypothesis. In this work, local distributions of deposited inhaled radon progenies in airway bifurcation models were computed at exposure conditions which are characteristic of homes and uranium mines. Then, maximum local deposition enhancement factors, that is, local per average deposition densities, were simulated, and the effects of the inhomogeneity of deposition on hit probabilities were characterised. Our results suggest that in the vicinity of the carinal regions of the central airways the probability of multiple hits can be quite high even at low doses.

Local deposition distributions of inhaled radionuclides in the human tracheobronchial tree.

There is experimental evidence that bronchogenic carcinomas originate mainly at the carinal ridges of the large central airways, where primary hot spots of deposition have been found. However, current lung dosimetry models do not take into consideration the inhomogeneity of deposition within the airways. In this study, computed local distributions of deposited inhaled radionuclides such as radon progenies in morphologically realistic human airway bifurcation models are analysed for different flow rates and particle sizes. Then, local deposition enhancement factors, defined as the ratio of local to average deposition densities, are computed by scanning along the surface of the bifurcation with pre-specified surface area elements. Computed enhancement factors indicate that cells located at carinal ridges or at the inner sides of the progeny branches may receive localised doses which are two orders of magnitude higher than the average values.

Quantification of local deposition patterns of inhaled radon decay products in human bronchial airway bifurcations.

Aerosol deposition studies with tracheobronchial casts and models have demonstrated that inhaled particles are preferentially deposited within transitional bifurcation zones, exhibiting hot spots in the vicinity of carinal ridges. The goal of the present study is to quantify the inhomogeneity of theoretically predicted deposition patterns by local deposition enhancement factors. First, inspiratory particle deposition patterns of unattached (1 nm), ultrafine (10 nm and 20 nm), and attached (100 nm and 200 nm) radon progeny within three-dimensional models of segmental bronchial airway bifurcations were simulated by a numerical fluid dynamics and particle trajectory model. Second, local deposition enhancement factors were computed by scanning along the surface of the bifurcation models with prespecified surface area elements. Maximum values and frequency distributions of local deposition enhancement factors of inhaled radon progeny were derived for different sizes of the scanning element in a "narrow" and a "physiologically realistic" bifurcation model and for two different flow rates (10 L min(-1) and 60 L min(-1) in the trachea). Computed enhancement factors indicate that cells located at carinal ridges may receive localized doses which are 20-40 times (1 nm) and 50-115 times higher (10 nm-200 nm), respectively, than the corresponding average doses. This may have important implications for the microdosimetry of inhaled radon progeny and the resulting lung cancer risk.