Significance of cell-cycle delay, multiple initiation pathways, misrepair and replication errors in a model of radiobiological effects.
OBJECTIVE
To advance a biomathematical model of radiocarcinogenesis by describing 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 irradiations of different cell lines and whether the fit parameters were then more biologically realistic.


METHODS
A biomathematical submodel was developed based on a previous State-Vector Model that mathematically described enhanced DNA repair and radical scavenging following irradiation.


RESULTS
With the two initiation pathways and cell-cycle delay, the simulations better explained the mouse data but not the rat data, and for both data sets the fit parameters were biologically more realistic than previously assumed. Inclusion of misrepair and replicational errors did not significantly affect the fit.


CONCLUSIONS
A plateau in the dose-effect relationship for in vitro irradiation of different cell lines can be explained by radioprotective mechanisms. The plateau-type dose-response relationships point to a non-linear dose- effect 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.
Schöllnberger
H
H
Lovelace Respiratory Research Institute, Albuquerque, NM 87185-5890, USA. hschollb@sph.unc.edu
Mebust
M R
MR
Crawford-Brown
D J
DJ
Eckl
P M
PM
Hofmann
W
W
D000818:Animals; D002453:Cell Cycle / Q000528:radiation effects*; D002869:Chromosome Aberrations; D004260:DNA Repair / Q000528:radiation effects*; D004261:DNA Replication / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D018499:Linear Energy Transfer; D051379:Mice; D008809:Mice, Inbred C3H; D051381:Rats; D011916:Rats, Inbred F344