Hypothesis: a unifying mechanism for nutrition and chemicals as lifelong modulators of DNA hypomethylation.
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.


CONCLUSIONS
Methyl groups from S-adenosylmethionine (SAM) are needed for DNA methylation. 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 glutathi-one (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 toxicologic responses.


CONCLUSIONS
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.
Lee
Duk-Hee
DH
Department of Preventive Medicine and Health Promotion Research Center, School of Medicine, Kyungpook National University, Daegu, Korea. lee_dh@knu.ac.kr
Jacobs
David R
DR
Porta
Miquel
M
D019175:DNA Methylation; D004785:Environmental Pollutants / Q000633:toxicity*; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D009747:Nutritional Physiological Phenomena; D009930:Organic Chemicals / Q000633:toxicity*
D004785:Environmental Pollutants; D009930:Organic Chemicals; D005978:Glutathione