%0 Journal Article
%T Nutritional Manipulation of One-Carbon Metabolism: Effects on Arsenic Methylation and Toxicity
%A Megan N. Hall
%A Mary V. Gamble
%J Journal of Toxicology
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/595307
%X 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. 1. Introduction Arsenic (As) is a naturally occurring element commonly present in environmental sources such as air, water, and soil [1]. Through processes that are incompletely understood, As in soil can be mobilized leading to enrichment of As in groundwater. While drinking water is the most common source of exposure, other sources include As from mining and smelting, wood preservatives, pesticides, and foods irrigated and/or prepared with As-contaminated water. Current estimates suggest that roughly 140 million people in Bangladesh, India, Vietnam, Nepal, and Cambodia are drinking water with As concentrations up to 100 times the World Health Organization (WHO) and USA Environmental Protection Agency (EPA) guideline of 10£¿¦Ìg/L [2, 3]. Chile, Mexico, China, and Taiwan also have As in groundwater that is used for drinking. In comparison to the situation in South and East Asia, the magnitude of the problem in the USA is relatively small. Nevertheless, the US Geological Survey estimates that 42 million Americans obtain their drinking water from household wells, and roughly 15% of these wells exceed the WHO guideline, indicating that a large number of USA residents are exposed to excess As from household wells [4]. In addition, not all municipalities are yet in compliance with the EPA requirements, with up to 8% of all public water supplies exceeding 10£¿¦Ìg As/L. Individuals chronically exposed to As are at increased risk for various cancers, including cancers of the skin (Bowen¡¯s disease,
%U http://www.hindawi.com/journals/jt/2012/595307/