Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Internet Explorer is no longer a supported browser.

This website may not display properly with Internet Explorer. For the best experience, please use a more recent browser such as the latest versions of Google Chrome, Microsoft Edge, and/or Mozilla Firefox. Thank you.

Your Environment. Your Health.

Progress Reports: Dartmouth College: Arsenic as an Endocrine Disrupter

Superfund Research Program

Arsenic as an Endocrine Disrupter

Project Leaders: Joshua W. Hamilton (Marine Biological Laboratory), Joshua W. Hamilton (Marine Biological Laboratory)
Grant Number: P42ES007373
Funding Period: 1995-2014

Learn More About the Grantee

Visit the grantee's eNewsletter page Visit the grantee's eNewsletter page Visit the grantee's Twitter page Visit the grantee's Facebook page Visit the grantee's Video page

Progress Reports

Year:   2013  2012  2011  2010  2009  2008  2007  2006  2005  2004  2003  2002  2001  2000  1999  1998  1997  1996  1995 

This project first discovered that arsenic can act as potent endocrine disruptor, and the current project continues to focus on two aspects of this effect. The first goal is to determine the mechanism(s) for these effects, focusing on the cellular and molecular level (Aims 1 and 2). The second goal (Aim 3) is to determine the adverse consequences of low dose arsenic exposure and how arsenic ultimately increases disease risk via endocrine disruption and other mechanisms at the physiological level. Dr. Joshua W. Hamilton’s research team has previously shown that arsenic profoundly affects the function of a wide variety of nuclear hormone receptors, making it a unique endocrine disruptor. It is likely, based on these results, that the mechanism for these arsenic effects involves a shared pathway or regulatory machinery given the diverse structures and functions of these receptors. The current project is focusing specifically on identifying the specific target(s) for these effects. Interestingly, at extremely low doses arsenic enhances hormone signaling (Aim 1) while at slightly higher but still relatively low doses, arsenic has the opposite effect and suppresses hormone signaling (Aim 2). The researchers hypothesize that these opposite effects involve separate mechanisms and distinct targets. Current work in Aims 1 and 2 is focused on two areas: the first is using a cell culture model system the group developed that allows them to determine whether arsenic alters the kinetics or function of nuclear hormone receptors using a photo-activatible GFP-tagged glucocorticoid receptor stably expressed in a human cell line (paGFP-GR-HEK cells). The second area is extending their work with specific receptors to focus on the PPAR receptor system and its regulation of lipid metabolism and adipocyte differentiation. The researchers have observed profound effects of low-dose arsenic on PPAR regulation of gene expression in response to hormone stimulation, and this results in changes in PPAR-mediated cell differentiation and lipid metabolism in cultured cells (FJ Zandbergen et al., manuscript in preparation 2011). Regarding Aim 3, the group recently observed effects of low-dose arsenic on growth and lipid homeostasis in the mothers and their newborn mice exposed to arsenic in vivo via drinking water to the mother (CD Kozul Horvath et al., manuscript submitted, 2011). The researchers have also seen profound effects of low-dose arsenic in drinking water on lipid regulation in adult male mice. Collectively, these results suggest that the broad endocrine disrupting abilities of arsenic in vivo result in specific patho-physiological effects at low doses as a consequence. These results are concordant with recent epidemiology studies indicating a link between arsenic exposure and metabolic disorders in human populations, and the group’s results with the pregnant female mice suggest that in utero and early childhood exposures may also result in metabolic disorders in the offspring.

Back
to Top