Multi-scaled Monte Carlo calculation for radon-induced cellular damage in the bronchial airway epithelium

AbstractRadon is a leading cause of lung cancer in indoor public and mining workers. Inhaled radon progeny releases alpha particles, which can damage cells in the airway epithelium. The extent and complexity of cellular damage vary depending on the alpha particle’s kinetic energy and cell characteristics. We developed a framework to quantitate the cellular damage on the nanometer and micrometer scales at different intensities of exposure to radon progenies Po-218 and Po-214. Energy depositions along the tracks of alpha particles that were slowing down were simulated on a nanometer scale using the Monte Carlo code Geant4-DNA. The nano-scaled track histories in a 5 μm radius and 1 μm-thick cylindrical volume were integrated into the tracking scheme of alpha trajectories in a micron-scale bronchial epithelium segment in the user-written SNU-CDS program. Damage distribution in cellular DNA was estimated for six cell types in the epithelium. Deep-sited cell nuclei in the epithelium would have less chance of being hit, but DNA damage from a single hit would be more serious, because low-energy alpha particles of high LET would hit the nuclei. The greater damage in deep-sited nuclei was due to the 7.69 MeV alpha particles emitted from Po-214. From daily work under 1 WL of radon concentration, basal cells would respond with the highest portion of complex DSBs among the suspected progenitor cells in the most exposed regions of the lung epithelium.

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Determination of CR-39 and LR-115 Type II Mean Critical Angle of Etching Using a New Monte Carlo Code

Journal of Nuclear Engineering and Radiation Science ◽

10.1115/1.4049343 ◽

2020 ◽

Author(s):

Hicham Harrass ◽

Abdellatif Talbi ◽

Rodouan Touti

Keyword(s):

Monte Carlo ◽

Alpha Particle ◽

Critical Angle ◽

Current Method ◽

Particle Energy ◽

Alpha Particles ◽

Monte Carlo Code ◽

Type Ii ◽

Alpha Particle Energy ◽

The Mean

Abstract CR-39 and LR-115 type II solid state nuclear track detectors (SSNTDs) are both used, in order to assess the concentration of nucleus belonging to 238U and 232Th series, these ones can be also used to measure radon 222Rn and thoron 220Rn gases in different locations. In this paper, a Monte Carlo code was developed to calculate the mean critical angle for which alpha particles emitted from 238U and 232Th families in studied material samples reach CR-39 and LR-115 type II surfaces and bring about latent tracks on them. The dependence of the SSNTDs mean critical angle on the removed thickness, the initial alpha particle energy has been studied. A linear relationship between CR-39 mean critical angle and the initial alpha particle energy for different removed thicknesses has been found. This straightforward relationship allows determining quickly the mean critical angle of etching which corresponds to initial alpha particle energy for a given removed thickness. CR-39 mean critical angle ranged from 59° for an alpha particle emitted by 212Po to 71° for an alpha particle emitted by 232Th, for the value of removed thickness of 6 µm; whereas LR-115 type II mean critical angle does not depend on the initial alpha particle energy except for 232Th, 238U, 230Th and 234Ra when the removed thickness ranged from 6 µm to 8 µm. Obtained data by using the current method and those obtained in the literature [18] are in good agreement with each other.

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Recoil proton, alpha particle, and heavy ion impacts on microdosimetry and RBE of fast neutrons: analysis of kerma spectra calculated by Monte Carlo simulation

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y00-088 ◽

2001 ◽

Vol 79 (2) ◽

pp. 189-195 ◽

Cited By ~ 2

Author(s):

Jean-Philippe Pignol ◽

Jakobus Slabbert

Keyword(s):

Monte Carlo ◽

Recoil Proton ◽

Clinical Results ◽

Heavy Ion ◽

Alpha Particles ◽

Fast Neutrons ◽

Monte Carlo Code ◽

Powerful Method ◽

Biological Effectiveness

Fast neutrons (FN) have a higher radio-biological effectiveness (RBE) compared with photons, however the mechanism of this increase remains a controversial issue. RBE variations are seen among various FN facilities and at the same facility when different tissue depths or thicknesses of hardening filters are used. These variations lead to uncertainties in dose reporting as well as in the comparisons of clinical results. Besides radiobiology and microdosimetry, another powerful method for the characterization of FN beams is the calculation of total proton and heavy ion kerma spectra. FLUKA and MCNP Monte Carlo code were used to simulate these kerma spectra following a set of microdosimetry measurements performed at the National Accelerator Centre. The calculated spectra confirmed major classical statements: RBE increase is linked to both slow energy protons and alpha particles yielded by (n,α) reactions on carbon and oxygen nuclei. The slow energy protons are produced by neutrons having an energy between 10 keV and 10 MeV, while the alpha particles are produced by neutrons having an energy between 10 keV and 15 MeV. Looking at the heavy ion kerma from <15 MeV and the proton kerma from neutrons <10 MeV, it is possible to anticipate y* and RBE trends.Key words: fast neutron, kerma, microdosimetry, RBE, Monte Carlo.

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Microarray analysis identifies defects in regenerative and immune response pathways in COPD airway basal cells

ERJ Open Research ◽

10.1183/23120541.00656-2020 ◽

2020 ◽

Vol 6 (4) ◽

pp. 00656-2020

Author(s):

Fanny Pineau ◽

Gabriella Shumyatsky ◽

Nicole Owuor ◽

Nisha Nalamala ◽

Sudhir Kotnala ◽

...

Keyword(s):

Epithelial Cell ◽

Microarray Analysis ◽

Airway Epithelium ◽

Bronchial Epithelium ◽

Basal Cells ◽

Airway Epithelial ◽

Tissue Development ◽

Epithelial Regeneration ◽

Copd Patients ◽

Response Expression

BackgroundAirway basal cells are specialised stem cells and regenerate airway epithelium. Airway basal cells isolated from patients with COPD regenerate airway epithelium with an abnormal phenotype. We performed gene expression analysis to gain insights into the defective regenerative programme in COPD basal cells.MethodsWe conducted microarray analysis and compared COPD versus normal basal cells to identify differentially regulated genes (DEGs) and the enriched biological pathways. We determined the correlation of DEGs with cell polarisation and markers of ciliated and goblet cells. HOXB2 was knocked down in 16HBE14o− cells and monitored for polarisation of cells. HOXB2 expression in the lung sections was determined by immunofluorescence.ResultsComparison of normal and COPD basal cell transcriptomic profiles highlighted downregulation of genes associated with tissue development, epithelial cell differentiation and antimicrobial humoral response. Expression of one of the tissue development genes, HOXB2 showed strong correlation with transepithelial resistance and this gene was downregulated in COPD basal cells. Knockdown of HOXB2, abrogated polarisation of epithelial cells in normal cells. Finally, HOXB2 expression was substantially reduced in the bronchial epithelium of COPD patients.ConclusionsDefect in gene signatures involved in tissue development and epithelial differentiation were implicated in COPD basal cells. One of the tissue developmental genes, HOXB2, is substantially reduced in bronchial epithelium of COPD patients. Since HOXB2 contributes to airway epithelial cell polarisation, we speculate that reduced expression of HOXB2 in COPD may contribute to abnormal airway epithelial regeneration in COPD.

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Early studies on the surface epithelium of mammalian airways

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00240.2019 ◽

2019 ◽

Vol 317 (4) ◽

pp. L486-L495 ◽

Cited By ~ 2

Author(s):

Jonathan H. Widdicombe

Keyword(s):

Airway Epithelium ◽

Mucociliary Clearance ◽

Cell Types ◽

Salt Transport ◽

Surface Epithelium ◽

Basal Cells ◽

Significant Progress ◽

Active Transfer ◽

Cholinergic Agents ◽

Physiological Research

This article traces the beginnings of the various areas of physiological research on airway epithelium. First mentioned in 1600, it was not until 1834 that it was found to be ciliated. Goblet and basal cells were described in 1852, to be followed by ~10 other epithelial cell types (the most recent in 2018). It also contains nerve endings and resident leukocytes. Mucociliary clearance was documented in 1835, but the first studies on the ciliary beat cycle did not appear until 1890, and a definitive description was not published until 1981. It was established in 1932 that goblet cells in the cat trachea were unresponsive to cholinergic agents; but only since 1980 or so has any significant progress been made on what does cause them to degranulate. Active transfer of salts across epithelia creates local osmotic gradients that drive transepithelial water flows. Vectorial salt transport was first described for airway epithelium in 1968, and the associated volume flows were measured in 1981. Evidence that airway epithelium releases signaling molecules first appeared in 1981. Since then, scores of molecules have been identified. The pace of research in most areas increased dramatically after the development of confluent, polarized cultures of airway epithelium in the early 1980s.

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The structure of the gills of the axolotl, Ambystoma mexicanum

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100128407 ◽

1987 ◽

Vol 45 ◽

pp. 824-825

Author(s):

Mohinder S. Jarial

Keyword(s):

Leydig Cells ◽

Secretory Granules ◽

Light And Electron Microscopy ◽

Cell Types ◽

Ambystoma Mexicanum ◽

Basal Cells ◽

Granular Cells ◽

Gill Filaments ◽

Mitotic Figures ◽

Apical Membranes

The axolotl is a strictly aquatic salamander in which the larval external gills are retained throughout life. The external gills of the adult axolotl have been studied by light and electron microscopy for ultrastructural evidence of ionic transport. The thin epidermis of the gill filaments and gill stems is composed of 3 cell types: granular cells, the basal cells and a sparce population of intervening Leydig cells. The gill epidermis is devoid of muscles, and no mitotic figures were observed in any of its cells.The granular cells cover the gill surface as a continuous layer (Fig. 1, G) and contain secretory granules of different forms, located apically (Figs.1, 2, SG). Some granules are found intimately associated with the apical membrane while others fuse with it and release their contents onto the external surface (Fig. 3). The apical membranes of the granular cells exhibit microvilli which are covered by a PAS+ fuzzy coat, termed “glycocalyx” (Fig. 2, MV).

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