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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 

Previously, investigators demonstrated that both chromium and arsenic alter expression of the model inducible gene, phosphoenolpyruvate carboxykinase (PEPCK), but through different mechanisms, and that this occurs at non-overtly toxic doses both in whole animals in vivo and in cells in culture. To examine these effects at the molecular level, researchers have designed and synthesized genetic constructs consisting of the PEPCK promoter DNA region linked to a reporter gene, and have shown that arsenic and chromium have strong, but differential effects on expression of this trans-gene at relatively low doses that are relevant to human exposures in the U.S. (i.e. through drinking water at the current standard for arsenic). The effects of arsenic and chromium on transcription factor activation are also being examined, and strong effects of each metal that are metal-, dose-, time-, and cell line-dependent have been shown . A collaboration is underway to examine involvement of specific cell signaling pathways in these processes. A sensitive molecular marker of heavy metal exposure is being developed for use in ecological field work based on changes in expression of marker proteins that are characteristic of exposure to specific heavy metals. Finally, similar molecular markers are being developed that could serve as sensitive and dose-dependent indicators of human exposure in the program's epidemiological study.

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