Explanation of protective effects of low doses of gamma-radiation with a mechanistic radiobiological model.
OBJECTIVE
To test whether data that show protective effects of low doses against spontaneous neoplastic transformation of C3H 10T1/2 cells can be explained with a biomathematical model that includes radioprotective mechanisms. To link important features of the model to known biological processes.


METHODS
The model simulates double-strand break formation in transcriptionally active and in bulk DNA, translocation of DNA segments, and the fixation of damage at mitosis; promotion is also included. The model equations were solved numerically using a stiff solver.


RESULTS
The data were successfully simulated by the model: cell transformation-reducing effects of low doses of gamma-radiation delivered at low dose-rates are explained by radiation-inducible DNA repair and enzymatic scavenging.


CONCLUSIONS
The model successfully simulates experimental data. The highly nonlinear features of the data point to a nonlinear dose-effect relationship at low doses and indicate that linear extrapolation from moderate (or high) to low doses and dose-rates may not be justified for in vitro studies of the cell line under consideration.
Schöllnberger
H
H
Institute of Physics and Biophysics, University of Salzburg, Hellbrunnerstr. 34, Austria. helmut.schoellnberger@sbg.ac.at
Mitchel
R E J
RE
Azzam
E I
EI
Crawford-Brown
D J
DJ
Hofmann
W
W
D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D007700:Kinetics; D051379:Mice; D008809:Mice, Inbred C3H; D008938:Mitosis / Q000528:radiation effects; D008962:Models, Theoretical; D011836:Radiation Tolerance; D013997:Time Factors
D004247:DNA