Repairdependent cell radiation survival and transformation: an integrated theory
Abstract
The repairdependent model of cell radiation survival is extended to include radiationinduced transformations. The probability of transformation is presumed to scale with the number of potentially lethal damages that are repaired in a surviving cell or the interactions of such damages. The theory predicts that at doses corresponding to high survival, the transformation frequency is the sum of simple polynomial functions of dose; linear, quadratic, etc, essentially as described in widely used linearquadratic expressions. At high doses, corresponding to low survival, the ratio of transformed to surviving cells asymptotically approaches an upper limit. The low dose fundamental and high dose plateau domains are separated by a downwardly concave transition region. Published transformation data for mammalian cells show the highdose plateaus predicted by the repairdependent model for both ultraviolet and ionizing radiation. For the neoplastic transformation experiments that were analyzed, the data can be fit with only the repairdependent quadratic function. At low doses, the transformation frequency is strictly quadratic, but becomes sigmodial over a wider range of doses. Inclusion of data from the transition region in a traditional linearquadratic analysis of neoplastic transformation frequency data can exaggerate the magnitude of, or create the appearance of, a linear component. Quantitative analysis of survival and transformation data shows good agreement for ultraviolet radiation; the shapes of the transformation components can be predicted from survival data. For ionizing radiations, both neutrons and xrays, survival data overestimate the transforming ability for low to moderate doses. The presumed cause of this difference is that, unlike UV photons, a single xray or neutron may generate more than one lethal damage in a cell, so the distribution of such damages in the population is not accurately described by Poisson statistics. However, the complete sigmodial doseresponse data for neoplastic transformations can be fit using the repairdependent functions with all parameters determined only from transformation frequency data.
 Publication:

Physics in Medicine and Biology
 Pub Date:
 September 2014
 DOI:
 10.1088/00319155/59/17/5073
 Bibcode:
 2014PMB....59.5073S