Project Summary (2008-2014)

The Epidemiology, Biomarkers and Exposure Assessment of Metals project is an integral component of the Dartmouth Superfund Basic Research Program (SBRP), focusing on the environmental and health impacts of toxic metal exposure in the U.S. Dr. Karagas' research team builds on 12 years of experience in designing and testing methods to measure environmentally relevant levels of exposure (and factors) that influence individual susceptibility to metal-related health effects.

Current accumulated data indicates that the developing fetus is particularly vulnerable to environmental insults, and these early life exposures impact childhood and adult health; as a result, scientists are testing the hypothesis that prenatal exposure to arsenic is associated with birth outcomes (e.g., birth weight, fetal growth restriction and gestational age) in New Hampshire. Scientists are also assessing whether individual variation in arsenic metabolism (based on maternal urinary metabolites and arsenic metabolism genes e.g., GSTO1, GSTO2, AS3T, PNP) and other factors (e.g., smoking, folate, or polymorphisms in one carbon metabolism genes) help to modify these effects. Scientists are evaluating the reliability of multiple measures of metal exposure (e.g., in drinking water, hair, nails and urine) within mothers and mother-infant pairs. Secondarily, they are investigating the hypothesis that methylmercury intake alone, or in combination with other factors, can influence fetal growth and gestational age.

Dr. Karagas's laboratory is conducting a collaborative analysis with the NIEHS-funded New Bedford birth cohort study (adjacent to a Superfund site) to increase statistical power.

Programatically, this project is:

1. Testing innovative strategies for the detection, characterization and interpretation of gene-environment interactions (with the Integrative Biology Core (IBC));
2. Exploring dietary sources and geographic patterns of metal exposure;
3. Providing a platform for translational molecular, genetic, and proteomic studies; and
4. Investigating the functional effects of polymorphisms in metal transporter genes.

Dr Karagas' laboratory is expanding collaborative and translational activities with other SBRPs, universities, and agencies. To date, this study is representative, i.e., among the first molecular epidemiologic investigations of early life exposure to arsenic and mercury in the U.S. population. The project's final goal is to inform, with regard to risk assessment and management, about the hazards of toxic metal exposure.