THE TESTING OF RADIOBIOLOGICAL MODELS OF RADON CARCINOGENESIS NEEDED FOR IN VITRO TO IN VIVO EXTRAPOLATIONS

摘要

Data on effects of radon stem from four levels of biological organization: in vitro irradiation of cell lines under uniform alpha flux; uniform irradiation of explants of groups of cells; non-uniform irradiation of lungs of organisms exposed to radon; and, irradiation of human populations with intra- and inter-subject variability of dose. Radon risk analysis must draw on these four levels of data. This requires theories of carcinogenesis providing understanding and prediction of effects at each level of organization, as well as the influence of the context of exposure. This paper presents a theoretical framework within which extrapolations between levels of organization can be performed. The framework allows determination of how findings at one level of organization provide information on 1) etiologic mechanisms, 2) mathematical forms of exposure-response relationships, and/or 3) values of parameters for extrapolations. This paper further explores how the theory brings data concerning DNA damage, sublesion interactions, DNA repair, mitotic rates, apoptotic rates, cytoxicity, intercellular communication, histology, anatomy, physiology, age, and concurrent exposures to bear on testing radiobiological models. The goal is to produce a theory by which assumptions concerning model form and parameter values are tested through data collected at all four levels of organization.