Nonlinear dose-response relationships and inducible cellular defence mechanisms.
With the inclusion of inducible radioprotective mechanisms in a radiobiological state-vector model it was possible to explain plateaus in dose-response relationships for neoplastic transformation produced by in vitro irradiation of different cell lines with low-LET irradiation at high dose rates. The current study repeated the simulation of one data set that contains a plateau at mid doses. In contrast to earlier studies, the new one did not model the repair of double-strand breaks (DSBs) located in bulk DNA (likely via non-homologous end joining) as being inducible. Repair of specific DSBs located in actively transcribed genes was assumed to occur via homologous recombination and was considered to be inducible. This reduced the number of parameters that have to be determined by fitting the model to data. In addition, all types of radical scavengers were formerly considered to be inducible by radiation. This was redefined in the current work and the effectiveness of scavengers was implemented in a refined way. The current work investigated whether these and other model adjustments lead to an improved fit of the data set.
Schöllnberger
Helmut
H
Institute of Physics and Biophysics, University of Salzburg, Austria.
Mitchel
Ron E
RE
Crawford-Brown
Douglas J
DJ
Hofmann
Werner
W
D000818:Animals; D002453:Cell Cycle / Q000528:radiation effects; D002460:Cell Line; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000528:radiation effects*; D004249:DNA Damage / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D016166:Free Radical Scavengers / Q000378:metabolism / Q000528:radiation effects; D018499:Linear Energy Transfer; D051379:Mice; D008962:Models, Theoretical
D016166:Free Radical Scavengers