Biophysical model for radiation carcinogenesis of inhaled radionuclides

Full text: A biophysical state-vector model (SVM) of radiation carcinogenesis has been developed which incorporates the stochasticity of cellular transitions and specific in vivo conditions in the lungs. Dose-rate dependent random transitions of cells between states of DNA strand breaks, interaction between breaks, fixation of damage, reversible and irreversible promotion, as well as cellular inactivation, damage repair and reversion of promoted cells are simulated by Monte Carlo methods. While most of the model parameters are developed directly from studies of the underlying processes, remaining parameters are constrained by fits to in vitro data on cellular radiation effects. At the tissue level, low doses of alpha particles are produced by a relatively small number of cellular hits, delivering, however, a rather high amount of energy to the nucleus of a traversed cell. To model alpha particle effects at the cellular level, the randomness of alpha particle interactions in a given cell nucleus was explicitly incorporated into the stochastic carcinogenesis model. The stochastic SVM was applied to predictions of lung cancer incidence in mining populations and in laboratory rats exposed to ambient radon progeny. When incorporating in vivo features of cell differentiation, stimulated mitosis and inhomogeneity of doses within bronchial epithelium, excellent agreement between epidemiological data and modelling predictions could be achieved. The model predicts a sub-linear dose response relationship, which is most significant at low doses and dose rates, suggesting that radon in homes may cause fewer lung cancers than currently predicted on the basis of the linear-no threshold (LNT) hypothesis. (author)