3D-modelling of radon-induced cellular radiobiological effects in bronchial airway bifurcations: Direct versus bystander effects

Szőke, István; Farkas, Árpád; Balásházy, Imre; Hofmann, Werner; Madas, Balázs G.; Szőke, Réka

doi:10.3109/09553002.2012.676229

Cited by 6 publications

(8 citation statements)

References 40 publications

(46 reference statements)

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“…Since experimentally determined radiobiological effects, such as cell killing, mutation and transformation are commonly expressed in terms of cellular doses, hit probabilities combined with average cellular doses are sometimes used to relate energy deposition at the cellular level to cellular radiobiological effects within lung tissue (Balásházy et al 2009;Hofmann et al 1990bHofmann et al , 1994Szőke et al 2006Szőke et al , 2009Szőke et al , 2012Truta-Popa et al 2011a). Although such simulations do not consider fluctuations of energy deposition within cells or cell nuclei, they are sometimes referred to as microdosimetric calculations.…”

Section: Microdosimetry Of Radon Progeny Alpha Particles In Bronchialmentioning

confidence: 99%

“…15 Comparison of simulated in vitro transformation frequencies per surviving cell of C3H 10T1/2 mouse embryo fibroblasts produced by a varying number of 5.3 MeV alpha particles with experimental data for microbeam and broad beam irradiation conditions. Adapted from approach was adopted by Szőke et al (2012) who combined track length distributions with experimentally derived cell killing and transformation functions based on average cellular doses to evaluate the contributions of bystander cells to the transformation probabilities in airway bifurcations as compared to direct hits. Distributions of transformed basal and secretory cells in a bronchial airway bifurcation model following exposure to radon progeny alpha particles for defined environmental and physiological inhalation conditions are plotted in Fig.…”

Section: Transformation Frequencymentioning

confidence: 99%

“…Distributions of transformed basal and secretory cells in a bronchial airway bifurcation model following exposure to radon progeny alpha particles for defined environmental and physiological inhalation conditions are plotted in Fig. 16 (Szőke et al 2012). Since multiple hits are associated with the hot spot activity distribution, the highest oncogenic risk can be observed around the carinal ridge.…”

Section: Transformation Frequencymentioning

confidence: 99%

“…16 Distribution of transformed basal and secretory cells in a bronchial airway bifurcation model following exposure to radon progeny alpha particles for defined environmental and physiological inhalation conditions, based on direct hits plus the indirect contribution of bystander cells. Adapted from Szőke et al (2012) the interaction is determined by the diffusion of sublesions within the cell over certain distances (distance model).…”

Section: The Theory Of Dual Radiation Actionmentioning

confidence: 99%

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Internal microdosimetry of alpha-emitting radionuclides

Hofmann

Friedland

et al. 2019

Radiat Environ Biophys

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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.

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Section: Microdosimetry Of Radon Progeny Alpha Particles In Bronchialmentioning

confidence: 99%

Section: Transformation Frequencymentioning

confidence: 99%

Section: Transformation Frequencymentioning

confidence: 99%

Section: The Theory Of Dual Radiation Actionmentioning

confidence: 99%

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Internal microdosimetry of alpha-emitting radionuclides

Hofmann

Friedland

et al. 2019

Radiat Environ Biophys

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“…On this basis the linear non-threshold model has been adopted to predict the possible lung carcinogenic effect even with very low doses from α-particles (National Research Council, 1999). Although the distribution of the α-particles and the location of the highly targeted areas in the respiratory system have already been suggested (National Research Council, 1999;Szőke et al, 2012), the biological mechanisms of the very early stages of α-particle-induced tumourigenesis remain elusive. Additionally the lung tissue may be exposed to low LET radiation during diagnostic X-ray examinations and radiotherapy (Hall and Brenner, 2008).…”

Section: Introductionmentioning

confidence: 99%

Lack of epithelial-to-mesenchymal transition induction in two bronchial epithelial cell lines after alpha and gamma irradiation

Acheva

Eklund

Lemola

et al. 2015

IJLR

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Abstract:The induction of epithelial-to-mesenchymal transition (EMT) in human lung epithelial cell lines was investigated after α-particle and γ-radiation exposures. We applied TGF-β treatment of cells as positive EMT-controls and tested in parallel if radiation has a potentiating effect on the EMT induction. BEAS-2B and HBEC-3KT cells were irradiated with 5.4 MeV α-particles or γ-rays ( 60 Co, 1.13-1.15 Gy/min) with or without of TGF-β. The cells were harvested three days post treatment and the EMT markers vimentin, fibronectin and E-cadherin were analysed by immunofluorescence staining and Western blotting. The TGF-β treatment-induced EMT in both cell lines in the applied concentrations. We could not prove any clear EMT induction with low or moderate doses of α-particles and γ-rays. No significant additive effect with radiation and TGF-β was observed. We suggest that there might be a different mechanism induced by radiation in bronchial cells after radon and medical exposures that does not involve direct EMT changes.

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

Madas

Boei

Fenske

et al. 2022

Radiat Environ Biophys

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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.

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3D-modelling of radon-induced cellular radiobiological effects in bronchial airway bifurcations: Direct versus bystander effects

Abstract: Our results are very sensitive to the radiobiological parameters, derived from in vitro experiments (e.g., range of bystander signalling), applied in this work and suggest that these parameters may not be directly applicable to realistic three-dimensional (3D) epithelium models.

Cited by 6 publications

References 40 publications

Internal microdosimetry of alpha-emitting radionuclides

Internal microdosimetry of alpha-emitting radionuclides

Lack of epithelial-to-mesenchymal transition induction in two bronchial epithelial cell lines after alpha and gamma irradiation

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

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