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

TL;DR

This study uses biophysical models to quantify how inhaled radon progeny influence different stages of lung carcinogenesis, highlighting their significant effects on mutation and clonal growth rates.

Contribution

It introduces a biophysical modeling approach to differentiate radon effects on initiation, transformation, and promotion in lung cancer development.

Findings

Initiation and transformation rates increase with dose rate

Effective promotion rate decreases over time but rises with dose rate

Radon effects on mutational events and clonal growth are significant

Abstract

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 objective 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, while effective promotion rate decreases with time, but increases in a supralinear fashion with dose rate. Despite the uncertainty of the 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 epidemiological analyses applying mathematical models of carcinogenesis.