  Applying the two-stage clonal expansion model to epidemiology of lung cancer
among uranium miners, it has been revealed that radon acts as a promoting agent
facilitating the clonal expansion of already mutated cells. Clonal expansion
rate increases non-linearly by radon concentration showing a plateau above a
given exposure rate. The underlying mechanisms remain unclear. Earlier we
proposed that progenitor cell hyperplasia may be induced upon chronic radon
exposure. The objective of the present study is to test whether the induction
of hyperplasia may provide a quantitative explanation for the plateau in clonal
expansion rate. For this purpose, numerical epithelium models were prepared
with different number of basal cells. Cell nucleus hits were computed by an
own-developed Monte-Carlo code. Surviving fractions were estimated based on the
number of cell nucleus hits. Cell division rate was computed supposing
equilibrium between cell death and cell division. It was also supposed that
clonal expansion rate is proportional to cell division rate, and therefore the
relative increase in cell division rate and clonal expansion rate are the same
functions of exposure rate. While the simulation results highly depend on model
parameters with high uncertainty, a parameter set has been found resulting in a
cell division rate exposure rate relationship corresponding to the plateau in
clonal expansion rate. Due to the high uncertainty of the applied parameters,
however, further studies are required to decide whether the induction of
hyperplasia is responsible for the non-linear increase in clonal expansion rate
or not. Nevertheless the present study exemplifies how computational modelling
can contribute to the integration of observational and experimental radiation
protection research.
