39 research outputs found
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, numerical epithelium models were generated 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 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...Comment: 13 pages, 5 figures, 1 tabl
Non-linear relationship of cell hit and transformation probabilities in a low dose of inhaled radon progenies
Cellular hit probabilities of alpha particles emitted by inhaled radon progenies in sensitive bronchial epithelial cell nuclei were simulated at low exposure levels to obtain useful data for the rejection or support of the linear-non-threshold (LNT) hypothesis. In this study, local distributions of deposited inhaled radon progenies in airway bifurcation models were computed at exposure conditions characteristic of homes and uranium mines. Then, maximum local deposition enhancement factors at bronchial airway bifurcations, expressed as the ratio of local to average deposition densities, were determined to characterise the inhomogeneity of deposition and to elucidate their effect on resulting hit probabilities. The results obtained 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 average doses. Assuming a uniform distribution of activity there are practically no multiple hits and the hit probability as a function of dose exhibits a linear shape in the low dose range. The results are quite the opposite in the case of hot spots revealed by realistic deposition calculations, where practically all cells receive multiple hits and the hit probability as a function of dose is non-linear in the average dose range of 10–100 mGy
The role of bronchial mucus layer thickness in radon dosimetry.
Abstract
Radon is considered to be the second most important cause of lung cancer after smoking. Several investigations proved that at radon inhalation the most exposed parts
are the central airways especially the carinal regions of these bifurcations. The radon progenies induced lung tumours show similar spatial distribution as the deposition
density distribution of inhaled radon progenies. The bronchial mucus layer absorbs a significant part of the energy of the ionizing alpha-particles. Since the mucus layer thickness is not constant in the different airway generations, the microdosimetric parameters can be significantly influenced by the mucus thickness. Hence, it may be quite important to investigate the role of mucus layer thickness in radon microdosimetry, what is the main objective of this research.
The major conclusions of this research are that the thickness of the mucus layer can basically influence the risk of inhaled radon progenies and the relationship between risk and exposure is slightly under linear in the analysed dose range applying an Initiation-Promotion Approach on a three-dimensional epithelium model. The effect of mucus thickness can be observed in every analysed microdosimetric quantities, hence mucus layer thickness cannot be neglected in radon dosimetry in the central airways
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, numerical 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.Comment: paper presented in the 17th International Symposium on Microdosimetry
(MICROS 2017 - Venice, Italy, 5-10 November, 2017), 5 pages, 1 table, 6
figure
Centrális légúti radondepozíció és tisztulás
Abstract
Most of the lung cancers of former uranium miners developed in the large central airways.
Current computational fluid dynamics calculations indicate high primary deposition in this region. However, the cellular burden of the radon progenies deposited in the deep
regions of the lung and clears up by the mucus layer may contribute to the health effects found in airway generations 2–5.
In this work, the deposition distribution of inhaled radon progenies was computed by a developed version of the stochastic lung model. A clearance model was constructed
to simulate the up clearing fractions of attached and non-attached radon progenies in each bronchial airway generations. Finally, the ratio of the primarily deposited and the up cleared fraction has been calculated in airway generation level at different breathing patterns and mucus velocities. The characteristic input data of the clearance model are the deposition pattern, the velocity of the mucus per generation, the length of the airways and the half life of radon progenies. Based on the results, in the central airways, the radiation burden of the up clearing,
more deeply deposited, radon progenies can significantly be higher than the burden of the primarily deposited fraction in these central airways