The goal is to conduct innovative, multidisciplinary research to identify the major sources of As and Hg exposure and to elucidate the protracted effects of early life exposure to As and Hg on human health. The ATSDR has identified As and Hg as the number one and number three environmental chemicals of concern with regard to human health. As exposure in the young increases the rates of diabetes, respiratory disease, and reproductive and developmental disorders. Methylmercury (MeHg) is a major contaminant in the food supply, particularly fish. For fetuses, infants, and children, exposure to MeHg has severe, adverse effects on the developing nervous system and interferes with cognitive thinking and memory. Despite growing concern and increasing research focus on As and Hg, there are significant knowledge gaps, especially with regard to very low levels of exposure in the US. Accordingly, the Dartmouth SRP is dedicated to obtaining new information on the effects of exposure to very low levels of As and Hg and thereby provide a foundation for science-based risk assessment leading to more informed, effective and comprehensive public health policies.
The specific aims are to: (1) Elucidate how As is taken up and accumulated in rice and to use this information to identify new rice cultivars that assimilate lower amounts of arsenic;(2) Elucidate how MeHg accumulates in fish and how environmental changes in temperature, salinity, and carbon content influences MeHg in marine ecosystems;(3) Identify the dose dependent and relative effects of inorganic and organic As on the innate immune response of the lung to bacterial infections;and (4) Understand the effects of maternal and fetal As exposure on the development of metabolic syndrome and inflammation in mothers and newborns, the most at risk in our population. The research will be supported by a Training Core, a Trace Elements Analysis Core, and the Research Translation and Community Engagement Cores that will communicate our research findings to our stakeholders and communities, respectively.

Public Health Relevance

The Dartmouth Superfund Research Program will conduct studies to determine how two of the most dangerous toxins in the environment lead to long-term deleterious health consequences, to develop innovative models for understanding the fetal basis of adult disease as it relates to in utero As exposure, and to integrate this knowledge with mechanistic information, and with exposure assessment information to understand the effects of As and Hg on human health. INDIVIDUAL RESEARCH PROJECTS PROJECT 1: Arsenic Uptake, Transport and Storage in Plants (Guerinot) DESCRIPTION (provided by applicant) Rice (Oryza sativa), a staple food for over half the world's population, represents a significant dietary source of inorganic arsenic (As), a non-threshold, class 1 human carcinogen. It is imperative that strategies to reduce grain As are developed, and establishing the mechanisms that enable As to reach and accumulate within the rice grain is key to this endeavor. This project will elucidate the genetic control of As homeostasis in plants to enable the development of plants that do not accumulate As. The first specific aim tests the hypothesis that genetic diversity in rice can be exploited to lower grain As levels by mapping genes in accessions known to vary in grain As content. The second aim asks more generally what genes are involved in transferring As to the grain and the third aim tests strategies to limit the movement o As to the shoot/grain based on information gained from study of rice, Arabidopsis and the As accumulating fern Pteris vittata. The long-term goal is to prevent As accumulation in the edible portion of rice grain, but the work will also potentially provide information on genes responsible for transporting As and other contaminant metal(loid)s into the tissues of other edible plant organs. In addition to identifying the causal loci, synchrotron X-ray fluorescence microanalysis (SXRF) will be used to precisely localize and speciate As in plants, an innovative approach that has been used successfully to examine seed loading of As. Public Health Relevance: The investigators'efforts to select rice cultivars that restrict As accumulation in the grain offers one of the simplest and most cost effective approaches to solving the problem of As contamination of rice and rice-based products. These cultivars could immediately be used in As contaminated regions, as well as being suitable genetic stock for breeding programs to introduce low grain As into varieties suitable for commercial rice production.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
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Special Emphasis Panel (ZES1)
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Carlin, Danielle J
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Dartmouth College
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