• OpenAccess
  • Mathematical Modeling of a Metabolic Network to Study the Impact of Food Contaminants on Genomic Methylation and DNA Instability  [GC 2014]
  • DOI: 10.4236/jbm.2014.210001   PP.1 - 7
  • Author(s)
  • Etienne Z. Gnimpieba, Souad Bousserouel, Abalo Chango
  • 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.

  • DNA-Methylation, DNA Instability, Mathematical Modeling, Logic Programming, Metabolic Network, Food Contaminant
  • References
  • [1]
    Duthie, S.J., Narayanan, S., Brand, G.M. and Grant, G. (2000) DNA Stability and Genomic Methylation Status in Colonocytes Isolated from Methyl-Donor-Deficient Rats. European Journal of Nutrition, 39, 106-111.
    Friso, S. and Choi, S.W. (2002) Gene-Nutrient Interactions and DNA Me-thylation. Journal of Nutrition, 132, 2382S- 2387S.
    Gabriel, H.E., Crott, J.W., Ghandour, H., Dallal, G.E., Choi, S.W., Keyes, M.K., Jang, H., Liu, Z., Nadeau, M., Johnston, A., Mager, D. and Mason, J.B. (2006) Chronic Cigarette Smoking Is Associated with Diminished Folate Status, Altered Folate Form Distribution, and Increased Genetic Damage in the Buccal Mucosa of Healthy Adults. The Ame- rican Journal of Clinical Nutrition, 83, 835-841.
    Toyota, M. and Suzuki, H. (2010) Epigenetic Drivers of Genetic Alterations. Advances in Genetics, 70, 309-323.
    Blount, B.C., Mack, M.M., Wehr, C.M., MacGregor, J.T., Hiatt, R.A., Wang, G., Wickramasinghe, S.N., Everson, R.B. and Ames, B.N. (1997) Folate Deficiency Causes Uracil Mis-incorporation into Human DNA and Chromosome Breakage: Implications for Cancer and Neuronal Damage. Proceedings of the National Academy of Sciences of the USA, 94, 3290-3295.
    Chango, A., Abdel Nour, A.M., Niquet, C. and Tessier, F.J. (2009) Simultaneous Determination of Genomic DNA Methylation and Uracil Misincorporation. Medical Principles and Practice, 18, 81-84.
    James, S.J., Pogribny, I.P., Pogribna, M., Miller, B.J., Jernigan, S. and Melnyk, S. (2003) Mechanisms of DNA Damage, DNA Hypomethylation, and Tumor Progression in the Folate/Methyl-Deficient Rat Model of Hepatocarcinogenesis. Journal of Nutrition, 133, 3740S-3747S.
    Ross, S.A. and Poirier, L. (2002) Proceedings of the Trans-HHS Workshop: Diet, DNA Methylation Processes and Health. Journal of Nutrition, 132, 2329S-2332S.
    Poirier, L.A. (2002) The Effects of Diet, Genetics and Chemicals on Toxicity and Aberrant DNA Me-thylation: An Introduction. Journal of Nutrition, 132, 2336S-2339S.
    Abdel Nour, A.M., Ringot, D., Gueant, J.L. and Chango, A. (2007) Folate Receptor and Human Reduced Folate Carrier Expression in HepG2 Cell Line Exposed to Fumonisin B1 and Folate Deficiency. Carcinogenesis, 28, 2291-2297.
    Lawley, S.D., Cinderella, M., Hall, M.N., Gamble, M.V., Nijhout, H.F. and Reed, M.C. (2011) Mathematical Model Insights into Arsenic Detoxification. Theoretical Biology and Medical Modelling, 8, 31.
    Gnimpieba, E.Z., Eveillard, D., Gueant, J.L. and Chango, A. (2011) Using Logic Programming for Modeling the One- Carbon Metabolism Network to Study the Impact of Folate Deficiency on Me-thylation Processes. Molecular BioSystems, 7, 2508-2521.
    Baccarelli, A. and Bollati, V. (2009) Epigenetics and Environmental Chemicals. Current Opinion in Pediatrics, 21, 243-251.
    Chango, A., Bousserouel, S., Ge, Z., Abdel Nour, A.N.N. and Ab-dennebi-Najar, L. (2011) Effects of Arsenic Exposure and Folate Deficiency on Methyl Metabolism in Human Fibroblast Cell Lines. The FASEB Journal, 25, 592-598.
    Chango, A., Nour, A.A., Bousserouel, S., Eveillard, D., Anton, P.M. and Gueant, J.L. (2009) Time Course Gene Expression in the One-Carbon Metabolism Network Using HepG2 Cell Line Grown in Folate-Deficient Medium. The Journal of Nutritional Biochemistry, 20, 312-320.
    Kagan, K.O., Avgidou, K., Molina, F.S., Gajewska, K. and Nicolaides, K.H. (2006) Relation between Increased Fetal Nuchal Translucency Thickness and Chromosomal Defects. Obstetrics Gyne-cology, 107, 6-10.
    Mihai, D., Niculescu, M.D. and Zeisel, S.H. (2002) Diet, Methyl Donors and DNA Methylation: Interactions between Dietary Folate, Methionine and Choline. Journal of Nutrition, 132, 2333S-2335S.
    Nijhout, H.F., Reed, M.C., Anderson, D.F., Mattingly, J.C., James, S.J. and Ulrich, C.M. (2006) Long-Range Allosteric Interactions between the Folate and Methionine Cycles Stabilize DNA Methylation Reaction Rate. Epigenetics, 1, 81-87.

Engineering Information Institute is the member of/source content provider to