Biophysical modelling of the effects of inhaled radon progeny on the bronchial epithelium for the estimation of the relationships applied in the two-stage clonal expansion model of carcinogenesis.

There is a considerable debate between research groups applying the two-stage clonal expansion model for lung cancer risk estimation, whether radon exposure affects initiation and transformation or promotion. The aim of the present study is to quantify the effects of radon progeny on these stages with biophysical models. For this purpose, numerical models of mutation induction and clonal growth were applied in order to estimate how initiation, transformation and promotion rates depend on tissue dose rate. It was found that rates of initiation and transformation increase monotonically with dose rate, whereas effective promotion rate decreases with time but increases sublinearly with dose rate. Despite the uncertainty of results due to the lack of experimental data, present study suggests that effects of radon exposure on both mutational events and clonal growth are significant and should be considered in mechanistic models of carcinogenesis applied for analysing epidemiological data.