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

Abstract

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.

Keywords::

• Radon inhalation
• lung microdosimetry
• mechanistic modelling
• bystander effects