A biokinetic model to describe consequences of inhibition/stimulation in DNA-proofreading and repair - 1. Development of the model

Authors
Citation
H. Haschke, A biokinetic model to describe consequences of inhibition/stimulation in DNA-proofreading and repair - 1. Development of the model, J THEOR BIO, 212(4), 2001, pp. 425-456
Citations number
29
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Multidisciplinary
Journal title
JOURNAL OF THEORETICAL BIOLOGY
ISSN journal
0022-5193 → ACNP
Volume
212
Issue
4
Year of publication
2001
Pages
425 - 456
Database
ISI
SICI code
0022-5193(20011021)212:4<425:ABMTDC>2.0.ZU;2-B
Abstract
A biokinetic model is described which deals with the mathematical consequen ces of the inhibition or stimulation of DNA proofreading. It demonstrates t he development of the number of DNA mismatch-dependent cells (e.g. cells wi th a malignant phenotype), where such mismatches arise by the in situ inter action of various substances with nucleotides of the DNA. The model can tes t for consequences by a logic gating on an "if-then" type of analysis in re lation to the separate and consecutive processes of proofreading and repair . In particular, the consequences are considered in cases where either (i) the efficacy of proofreading and repair are reduced/prevented (inhibited) o r (ii) are increased by some form of stimulation. On the chosen kinetic par ameters, the model is accessible to manipulation as new data arising from f urther investigations become available and are introduced. The model is bas ed on recently published data which show that an increased "mutant fraction " (see note on terms) arises in DNA replication when intracellular nucleoti de pools show "asymmetries" (see note on terms). Extraordinarily high mutan t fractions can be predicted/have been recorded in the presence of proofrea ding inhibitors. The model expresses data in mathematical terms of the comp etition between the development of mismatch-dependent cells and those with authentic genetic information. (Feedback and metastasis-effects and those o f wild-type replicates are included.) A computerized (numerical) integratio n of the corresponding set of differential equations is offered. (A diskett e with the program CANCER.xls is available upon request.) (C) 2001 Academic Press.