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

PURPOSE: The primary objective of this paper was to investigate the distribution of radiation doses and the related biological responses in cells of a central airway bifurcation of the human lung of a hypothetical worker of the New Mexico uranium mines during approximately 12 hours of exposure to short-lived radon progenies. MATERIALS AND METHODS: State-of-the-art computational modelling techniques were applied to simulate the relevant biophysical and biological processes in a central human airway bifurcation. RESULTS: The non-uniform deposition pattern of inhaled radon daughters caused a non-uniform distribution of energy deposition among cells, and of related cell inactivation and cell transformation probabilities. When damage propagation via bystander signalling was assessed, it produced more cell killing and cell transformation events than did direct effects. If bystander signalling was considered, variations of the average probabilities of cell killing and cell transformation were supra-linear over time. CONCLUSIONS: 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.

Size distribution, pulmonary deposition and chemical composition of Hungarian biosoluble glass fibers.

Compared to spherical particles, inhaled fibers may cause enhanced adverse health effects because of their specific shape, thus acting as so-called physical carcinogens. The chemical composition of fibers plays a determining role on the durability and hence may play a potential role in related health effects due to their toxic components. The physical properties, that is, length, diameter, and size distribution, and the chemical composition of fiberglass materials sampled at a Hungarian glass wool factory were investigated. The morphology of the particles was studied by optical microscopy and scanning electron microscopy (SEM), while for the chemical analysis instrumental neutron activation analysis (INAA) and SEM combined with energy-dispersive x-ray analysis (EDX) were used. Deposition fractions of the fibers in different regions of the lung and in the whole human respiratory system were computed by a stochastic lung deposition model for different flow rates and equivalent diameters, using experimentally determined size distributions.

Alpha-hit, cellular dose, cell transformation and inactivation probability distributions of radon progenies in the bronchial epithelium.

A fluid dynamics based model has been used to determine the deposition patterns of inhaled radon daughters in a realistic approach of the bronchial airway geometry. The interaction of the emitted alpha particles with epithelial cells has been analyzed by applying a complex hit probability model (Bronchial Alpha Hit Model). The biological response of the hit cells has been calculated by the Probability-Per-Unit-Track-Length Model, which relates the probability of a specific biological effect to the track length of alpha particles as a function of the particles' LET. The models mentioned above form a complex lung-radon interaction description. The calculations indicate that compared to the average values the transformation and cell killing probabilities are higher at bronchial carinal ridges. In addition, a considerable number of cells possessing a not negligible transformation and cell killing probabilities can also be found in the outer sides of the central zone.

Simulation of fiber deposition in bronchial airways.

Penetration probabilities of inhaled man-made mineral fibers to reach central human airways were computed by a stochastic lung deposition model for different flow rates and equivalent diameters. Results indicate that even thick and long fibers can penetrate into the central airways at low flow rates. Deposition efficiencies and localized deposition patterns were then computed for man-made fibers with variable lengths in a three-dimensional physiologically realistic bifurcation model of the central human airways by computational fluid dynamics (CFD) techniques for characteristic breathing patterns. The results obtained for inspiratory flow conditions indicate that deposition efficiencies were highest for parallel orientation of the fibers, increasing with rising flow rate, branching angle, and fiber length at all orientations. Furthermore, deposition patterns were highly inhomogeneous and their localized distributions showed hot spots in the vicinity of the carinal ridge and at the inner sides of the daughter airways. Comparisons with other theoretical results demonstrate that the equivalent diameter concept, if including interception, presents a reasonable approximation for the parameter ranges employed in the present study.