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Journal of Toxicology
Volume 2012, Article ID 595307, 11 pages
Review Article

Nutritional Manipulation of One-Carbon Metabolism: Effects on Arsenic Methylation and Toxicity

1Department of Epidemiology, Mailman School of Public Health, Columbia University, 722 West 168th Street, Room T31, New York, NY 10032, USA
2Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 722 West 168th Street, Room 1107E, New York, NY 10032, USA

Received 15 June 2011; Revised 20 December 2011; Accepted 21 December 2011

Academic Editor: Tanja Schwerdtle

Copyright © 2012 Megan N. Hall and Mary V. Gamble. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Exposure to arsenic (As) through drinking water is a substantial problem worldwide. The methylation of As, a reactive metalloid, generates monomethyl- (MMA) and dimethyl-arsenical (DMA) species. The biochemical pathway that catalyzes these reactions, one-carbon metabolism, is regulated by folate and other micronutrients. Arsenic methylation exerts a critical influence on both its urinary elimination and chemical reactivity. Mice having the As methyltransferase null genotype show reduced urinary As excretion, increased As retention, and severe systemic toxicity. The most toxic As metabolite in vitro is M M A I I I , an intermediate in the generation of D M A V , a much less toxic metabolite. These findings have raised the question of whether As methylation is a detoxification or bioactivation pathway. Results of population-based studies suggest that complete methylation of inorganic As to DMA is associated with reduced risk for As-induced health outcomes, and that nutrients involved in one-carbon metabolism, such as folate, can facilitate As methylation and elimination.