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Journal of Nucleic AcidsVolume 2010 2010, Article ID 352603, 7 pages

Research Article

Department of Mathematics, Vanderbilt University, Nashville, TN 37240, USA

Department of Pathology, Vanderbilt University, Nashville, TN 37232, USA

Received 13 April 2010; Accepted 27 May 2010

Academic Editor: Ashis Basu

Copyright © 2010 Philip S. Crooke and Fritz F. Parl. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

In cells, DNA repair has to keep up with DNA damage to maintain the integrity of the genome and prevent mutagenesis and carcinogenesis. While the importance of both DNA damage and repair is clear, the impact of imbalances between both processes has not been studied. In this paper, we created a combined mathematical model for the formation of DNA adducts from oxidative estrogen metabolism followed by base excision repair BER of these adducts. The model encompasses a set of differential equations representing the sequence of enzymatic reactions in both damage and repair pathways. By combining both pathways, we can simulate the overall process by starting from a given time-dependent concentration of 17-estradiol and -deoxyguanosine, determine the extent of adduct formation and the correction by BER required to preserve the integrity of DNA. The model allows us to examine the effect of phenotypic and genotypic factors such as different concentrations of estrogen and variant enzyme haplotypes on the formation and repair of DNA adducts.





Autor: Philip S. Crooke and Fritz F. Parl

Fuente: https://www.hindawi.com/



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