The effect of the G1-S transition checkpoint on an age structured cell cycle model.

Chaffey, Gary, Lloyd, David, Skeldon, Anne and Kirkby, Norman (2014) The effect of the G1-S transition checkpoint on an age structured cell cycle model. PLoS One, 9 (1), e83477.

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Abstract

Knowledge of how a population of cancerous cells progress through the cell cycle is vital if the population is to be treated effectively, as treatment outcome is dependent on the phase distributions of the population. Estimates on the phase distribution may be obtained experimentally however the errors present in these estimates may effect treatment efficacy and planning. If mathematical models are to be used to make accurate, quantitative predictions concerning treatments, whose efficacy is phase dependent, knowledge of the phase distribution is crucial. In this paper it is shown that two different transition rates at the G1-S checkpoint provide a good fit to a growth curve obtained experimentally. However, the different transition functions predict a different phase distribution for the population, but both lying within the bounds of experimental error. Since treatment outcome is effected by the phase distribution of the population this difference may be critical in treatment planning. Using an age-structured population balance approach the cell cycle is modelled with particular emphasis on the G1-S checkpoint. By considering the probability of cells transitioning at the G1-S checkpoint, different transition functions are obtained. A suitable finite difference scheme for the numerical simulation of the model is derived and shown to be stable. The model is then fitted using the different probability transition functions to experimental data and the effects of the different probability transition functions on the model's results are discussed.

Item Type:	Article
Divisions :	Faculty of Engineering and Physical Sciences > Mathematics
Authors :	Name Email ORCID Chaffey, Gary gary.chaffey@surrey.ac.uk Lloyd, David D.J.Lloyd@surrey.ac.uk Skeldon, Anne A.Skeldon@surrey.ac.uk Kirkby, Norman N.Kirkby@surrey.ac.uk
Date :	2014
DOI :	10.1371/journal.pone.0083477
Copyright Disclaimer :	Copyright 2014 Chaffey et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Related URLs :	Author
Depositing User :	Symplectic Elements
Date Deposited :	08 May 2014 10:54
Last Modified :	06 Jul 2019 05:13
URI:	http://epubs.surrey.ac.uk/id/eprint/805502

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