Modulators of DNA Hypomethylation
Full Text: http://www.ehponline.org/members/2009/0900741/0900741.pdf
Duk-Hee Lee, David R Jacobs, Jr., Miquel Porta
doi: 10.1289/ehp.0900741 (available at http://dx.doi.org/)
Online 8 July 2009
ehponline.org
Abstract
Background: Although both nutrition and chemicals are important
environmental factors
modulating epigenetic changes, they are commonly studied separately by
researchers in
different fields. However, these two environmental factors cannot be
separated from each
other in the real world because a number of chemical agents contaminate food
chains.
Objective: We propose a unifying mechanism that can link epigenetic
alterations in
relation to DNA hypomethylation due to chemical agents and to nutrient
deficiency or
imbalance, emphasizing the importance of an integrative approach in the
field of
environmental epidemiology.
Discussion: Methyl groups from S-adenosylmethionine (SAM) are needed for DNA
methylation. Thus, diets low in sources of methyl groups can lead to global
DNA
hypomethylation by impairing synthesis of SAM. However, even without
nutritional
deficiency, enhanced need to synthesize glutathione (GSH) can impair
synthesis of SAM and
perturb DNA methylation, because the methylation cycle and the GSH synthesis
pathways
are biochemically linked. Exposure to environmental chemicals is a common
situation in
which the need for GSH synthesis is enhanced, because GSH is consumed to
conjugate
diverse chemicals. Given that GSH conjugation happens at any chemical dose,
this
hypothesis is relevant even at exposures below the high doses that cause
toxicological
responses.
Conclusion: At present, general populations are exposed to a large number of
chemicals,
each at a very low dose. Thus, DNA hypomethylation due to chemical exposure
may be
common in modern societies and can synergistically interact with
nutrition-induced DNA
hypomethylation.
