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Drinking-Water Arsenic Exposure Modulates Gene Expression In Human Lymphocytes From A U.S. Population, Angeline S. Andrew, David A. Jewell, Rebecca A. Mason, Michael L. Whitfield, Jason H. Moore, Margaret R. Karagas

Dartmouth Scholarship

Background:

Arsenic exposure impairs development and can lead to cancer, cardiovascular disease, and diabetes. The mechanism underlying these effects remains unknown. Primarily because of geologic sources of contamination, drinking-water arsenic levels are above the current recommended maximum contaminant level of 10 μg/L in the northeastern, western, and north central regions of the United States.

Objectives:

We investigated the effects of arsenic exposure, defined by internal biomarkers at levels relevant to the United States and similarly exposed populations, on gene expression.

Methods:

We conducted separate Affymetrix microarray-based genomewide analyses of expression patterns. Peripheral blood lymphocyte samples from 21 controls interviewed (1999–2002) …

Adenomatous Polyposis Coli Is Present Near The Minimal Level Required For Accurate Graded Responses To The Wingless Morphogen, Hassina Benchabane, Edward G. Hughes, Carter M. Takacs, Jason R. Baird, Yashi Ahmed

Dartmouth Scholarship

The mechanisms by which the Wingless (Wg) morphogen modulates the activity of the transcriptional activator Armadillo (Arm) to elicit precise, concentration-dependent cellular responses remain uncertain. Arm is targeted for proteolysis by the Axin/Adenomatous polyposis coli (Apc1 and Apc2)/Zeste-white 3 destruction complex, and Wg-dependent inactivation of destruction complex activity is crucial to trigger Arm signaling. In the prevailing model for Wg transduction, only Axin levels limit destruction complex activity, whereas Apc is present in vast excess. To test this model, we reduced Apc activity to different degrees, and analyzed the effects on three concentration-dependent responses to Arm signaling that specify distinct …