title: A computational model for radiation-induced cellular transformation to in vitro irradiation of cells by acute doses of X-rays.
abstract: This research incorporates new biological concepts to improve the predictive ability of a state-vector model with respect to dose-response data on in vitro oncogenic transformation, including mechanisms of DNA damage, DNA repair, cell death, cell proliferation and intercellular communication. Experimentally recognized biological processes, including background transformation, compensatory proliferation and bystander cell-killing effect were formulated mathematically and included as model parameters. These were then adjusted with an optimization method to reproduce in vitro transformation frequency data from C3H10T1/2 mouse cells exposed to acute doses of X-rays. A plateau observed in the data at low doses is reproduced well and a dose-dependent increase above 1 Gy is predicted almost precisely. Extension of the model predictions to the dose range 0-100 mGy indicates that transformation frequencies are practically constant over this low dose region. Results suggest a protective, rather than detrimental, bystander cell-killing effect. Further analysis of model sensitivity to this bystander parameter, though, revealed uncertainties with respect to its biological plausibility in the model.
authors.affiliation: Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: L
authors.initials: L
authors.lastname: Fleishman
authors.forename: D
authors.initials: D
authors.lastname: Crawford-Brown
authors.forename: W
authors.initials: W
authors.lastname: Hofmann