Project 4 is an integral component of the Dartmouth Superfund Basic Research Program (SBRP), focusing on the environmental and health impact of toxic metal exposure in the US. We propose to build on 12 years of experience designing and testing methods of measuring environmentally relevant levels of exposure and factors that influence individual susceptibility to metal-related health effects. Accumulating data point to the developing fetus as particularly vulnerable to environmental insults and that early life exposures impact childhood and adult health. Thus, we propose to test the hypothesis that prenatal exposure to arsenic is associated with birth outcomes (e.g., birth weight, fetal growth restriction and gestational age) in the New Hampshire population. We also will assess whether individual variation in arsenic metabolism (based on maternal urinary metabolites, arsenic metabolism genes e.g., GSTO1, GSTO2, AS3T, PNP) and other factors (e.g., smoking, folate or polymorphisms in one carbon metabolism genes) modify these effects. We will evaluate the reliability of multiple measures of metal exposure (e.g., in drinking water, hair, nails and urine) within mothers and in mother-infant pairs. Secondarily, we will investigate the hypothesis that methylmercury intake alone or in combination with other factors influences fetal growth and gestational age. We will conduct a collaborative analysis with the NIEHS-funded New Bedford birth cohort study (adjacent to a Superfund Site) to increase statistical power. Programatically, we will: (1) test innovative strategies for the detection, characterization and interpretation of gene-environment interactions (with the Integrative Biology Core (IBC)), (2) explore dietary sources and geographic patterns of metal exposure (with Projects 7, 9), (3) provide a platform for translational molecular, genetic, and proteomic studies (for the IBC, Projects 2, 7, 8, 9) and (4) investigate the functional effects of polymorphisms in metal transporter genes (with the IBC, Projects 8, 9). We will expand collaborative and translational activities with other SBRPs, universities and agencies. To our knowledge, the study proposed will represent among the first molecular epidemiologic investigations of early life exposure to arsenic and mercury in a general population of the US. Our goal is to inform risk assessment and management of toxic metal exposure in the US, and aid early intervention strategies to prevent adverse health effects from these exposures.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
5P42ES007373-18
Application #
8376735
Study Section
Special Emphasis Panel (ZES1-JAB-C)
Project Start
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
18
Fiscal Year
2012
Total Cost
$518,026
Indirect Cost
$169,052
Name
Dartmouth College
Department
Type
DUNS #
041027822
City
Hanover
State
NH
Country
United States
Zip Code
03755
Chu, Heng-Hsuan; Car, Suzana; Socha, Amanda L et al. (2017) The Arabidopsis MTP8 transporter determines the localization of manganese and iron in seeds. Sci Rep 7:11024
Baumann, Zofia; Mason, Robert P; Conover, David O et al. (2017) Mercury bioaccumulation increases with latitude in a coastal marine fish (Atlantic silverside, Menidia menidia). Can J Fish Aquat Sci 74:1009-1015
Lee, Cheng-Shiuan; Fisher, Nicholas S (2017) Bioaccumulation of methylmercury in a marine copepod. Environ Toxicol Chem 36:1287-1293
Taylor, Vivien F; Li, Zhigang; Sayarath, Vicki et al. (2017) Distinct arsenic metabolites following seaweed consumption in humans. Sci Rep 7:3920
Goodale, Britton C; Rayack, Erica J; Stanton, Bruce A (2017) Arsenic alters transcriptional responses to Pseudomonas aeruginosa infection and decreases antimicrobial defense of human airway epithelial cells. Toxicol Appl Pharmacol 331:154-163
Punshon, Tracy; Jackson, Brian P; Meharg, Andrew A et al. (2017) Understanding arsenic dynamics in agronomic systems to predict and prevent uptake by crop plants. Sci Total Environ 581-582:209-220
Farzan, Shohreh F; Brickley, Elizabeth B; Li, Zhigang et al. (2017) Maternal and infant inflammatory markers in relation to prenatal arsenic exposure in a U.S. pregnancy cohort. Environ Res 156:426-433
Cubadda, Francesco; Jackson, Brian P; Cottingham, Kathryn L et al. (2017) Human exposure to dietary inorganic arsenic and other arsenic species: State of knowledge, gaps and uncertainties. Sci Total Environ 579:1228-1239
Davis, Matthew A; Signes-Pastor, Antonio J; Argos, Maria et al. (2017) Assessment of human dietary exposure to arsenic through rice. Sci Total Environ 586:1237-1244
Martin, Elizabeth; Smeester, Lisa; Bommarito, Paige A et al. (2017) Sexual epigenetic dimorphism in the human placenta: implications for susceptibility during the prenatal period. Epigenomics 9:267-278

Showing the most recent 10 out of 335 publications