Mathematical Modeling of a Metabolic Network to Study the Impact of Food Contaminants on Genomic Methylation and DNA Instability

摘要

Environmental contamination of food is a worldwide public health problem. Folate mediated one- carbon metabolism plays an important role in epigenetic regulation of gene expression and mutagenesis. Many contaminants in food cause cancer through epigenetic mechanisms and/or DNA instability i.e. default methylation of uracil to thymine, subsequent to the decrease of 5-methylte- trahydrofolate (5 mTHF) pool in the one-carbon metabolism network. Evaluating consequences of an exposure to food contaminants based on systems biology approaches is a promising alternative field of investigation. This report presents a dynamic mathematical modeling for the study of the alteration in the one-carbon metabolism network by environmental factors. It provides a model for predicting “the impact of arbitrary contaminants that can induce the 5 mTHF deficiency. The model allows for a given experimental condition, the analysis of DNA methylation activity and dumping methylation in the de novo pathway of DNA synthesis.