H. Schollnberger et al., Significance of cell-cycle delay, multiple initiation pathways, misrepair and replication errors in a model of radiobiological effects, INT J RAD B, 77(4), 2001, pp. 519-527
Purpose: To advance a biomathematical model of radiocarcinogenesis by descr
ibing multiple pathways for initiation, a radiologically induced cell-cycle
delay, misrepair and spontaneous DNA damages caused by replication. It was
investigated whether the incorporation of these biological features would
improve the fit of the model to data showing plateaus in in vitro irradiati
ons of different cell lines and whether the fit parameters were then more b
iologically realistic.
Materials and methods: A biomathematical submodel was developed based on a
previous State-Vector Model that mathematically described enhanced DNA repa
ir and radical scavenging following irradiation.
Results: With the two initiation pathways and cell-cycle delay the simulati
ons better explained the mouse data but not the rat data, and for both data
sets the fit parameters were biologically more realistic than previously a
ssumed. Inclusion of misrepair and replicational errors did not significant
ly affect the fit.
Conclusions: A plateau in the dose-effect relationship for in vitro irradia
tion of different cell lines can be explained by radioprotective mechanisms
. The plateau-type dose-response relationships point to a non-linear dose-e
ffect relationship at low doses and indicate that linear extrapolation from
moderate (or high) to low doses may not be justified for in vitro studies
of these cell lines.