Prediction of lung cancer risk for radon exposures based on cellular alpha particle hits.

To explore the role of the multiplicity of cellular hits by radon progeny alpha particles for lung cancer incidence, the number of single and multiple alpha particle hits were computed for basal and secretory cells in the bronchial epithelium of human airway bifurcations. Hot spots of alpha particle hits were observed at the branching points of bronchial airway bifurcations. The effect of single and multiple alpha particle intersections of bronchial cells during a given exposure period, selected from a Poisson distribution, on lung cancer risk were simulated by a transformation frequency--tissue response model, based on experimentally observed cellular transformation and survival functions. Calculations of lung cancer risk at low radon exposure levels suggest that single hits produce a linear-dose response relationship, while the superposition of single and increasing multiple hits at higher exposure levels may also be approximated by a quasi-linear dose-effect curve. The simulations predict a carcinogenic enhancement effect for radon progeny accumulations at bifurcation branching sites, which may increase current risk estimates.