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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

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Progress Reports

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

Understanding the mechanistic basis for human health effects of heavy metals is critical for evaluating the impact of these exposures on the U.S. population, and is relevant to setting exposure standards. For example, is there a threshold dose, a linear dose-response or some other dose-response relationship for these endpoints? Do combinations of these metals have additive, synergistic, antagonistic, or entirely unpredictable biological effects? Can these effects be blocked with other agents?

The researchers are working at doses of these metals that are highly relevant to U.S. exposures. For example, the doses of arsenic being used fall roughly between the current arsenic drinking water standard of 50 ppm and the proposed new standard of 2 ppm. Thus, these mechanistic studies are relevant to understanding the overall human health impact of exposure to these metals and setting standards for exposure.

This project's scientists have most recently shown that the heavy metals, chromium and arsenic, which are human carcinogens, each have significant, but different, effects on critical cellular targets which regulate gene expression. These effects are metal-, dose-, time- and tissue type-specific, and appear to involve direct effects on both the genes themselves and on the proteins which regulate their expression. In a model system, the scientists have narrowed down the apparent targets for these effects to several small regions within their promoter control region of the affected genes, and to a small number of critical protein factors which regulate their expression through these sites. Further studies will be aimed at understanding precisely how chromium and arsenic affect gene expression through these targets, and the relevance of these effects to the cancer process and possibly other disease processes. These pathways may contribute to the overall carcinogenic and other biological effects of these metals.

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