Significance of cell-cycle delay, multiple initiation pathways, misrepair and replication errors in a model of radiobiological effects

Citation
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
Citations number
32
Categorie Soggetti
Experimental Biology
Journal title
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
ISSN journal
09553002 → ACNP
Volume
77
Issue
4
Year of publication
2001
Pages
519 - 527
Database
ISI
SICI code
0955-3002(200104)77:4<519:SOCDMI>2.0.ZU;2-A
Abstract
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.