Journal
ENVIRONMENTAL HEALTH PERSPECTIVES
Volume 117, Issue 12, Pages 1799-1802Publisher
US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
DOI: 10.1289/ehp.0900741
Keywords
chemicals; DNA hypomethylation; epigenetics; glutathione; nutrient; persistent organic pollutants
Funding
- Korean Healthcare Technology R&D Project, Ministry of Health, Welfare & Family Affairs, Republic of Korea [A084046]
- Korea Health Promotion Institute [A084046] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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. 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 die high doses that cause toxicologic responses. CONCLUSION: At present, general populations are exposed to a large number of chemicals, each at a very low dose. Thus, DNA hypornethylation due to chemical exposure may be common in modern societies and can synergistically interact with nutrition-induced DNA hypomethylation.
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