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ToxSci Advance Access originally published online on August 6, 2007
Toxicological Sciences 2007 100(1):75-87; doi:10.1093/toxsci/kfm200
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© The Author 2007. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Exposure to Arsenic at Levels Found in U.S. Drinking Water Modifies Expression in the Mouse Lung

Angeline S. Andrew*,{dagger},{ddagger},1, Viviane Bernardo§,¶, Linda A. Warnke||, Jennifer C. Davey{ddagger},|||, Thomas Hampton{ddagger},|||, Rebecca A. Mason*,|||, Jessica E. Thorpe||, Michael A. Ihnat|| and Joshua W. Hamilton{dagger},{ddagger},|||

* Department of Community and Family Medicine, Dartmouth Medical School, Lebanon, New Hampshire 03756 {dagger} Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03756 {ddagger} Center for Environmental Health Sciences, Dartmouth Medical School, Hanover, New Hampshire 03755 § Thayer School of Engineering/Computer Sciences Department, Dartmouth College, Hanover, New Hampshire 03755 Health Informatics Department, Federal University of Sao Paulo/Escola Paulista de Medicina-UNIFESP/EPM, Sao Paulo, SP, Brazil || Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73190 ||| Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire 03755

1 To whom correspondence should be addressed at Dartmouth Medical School, 7927 Rubin 860, One Medical Center Drive, Lebanon, NH 03756. Fax: (603) 653-9093. E-mail: angeline.andrew{at}dartmouth.edu.

Received April 6, 2007; accepted July 30, 2007


  Abstract

The mechanisms of action of drinking water arsenic in the lung and the threshold for biologic effects remain controversial. Our study utilizes Affymetrix 22,690 transcript oligonucleotide microarrays to assess the long-term effects of increasing doses of drinking water arsenic on expression levels in the mouse lung. Mice were exposed at levels commonly found in contaminated drinking water wells in the United States (0, 0.1, 1 ppb), as well as the 50 ppb former maximum contaminant level, for 5 weeks. The expression profiles revealed modification of a number of important signaling pathways, many with corroborating evidence of arsenic responsiveness. We observed statistically significant expression changes for transcripts involved in angiogenesis, lipid metabolism, oxygen transport, apoptosis, cell cycle, and immune response. Validation by reverse transcription–PCR and immunoblot assays confirmed expression changes for a subset of transcripts. These data identify arsenic-modified signaling pathways that will help guide investigations into mechanisms of arsenic's health effects and clarify the threshold for biologic effects and potential disease risk.

Key Words: arsenic; apoptosis; cell cycle; drinking water; immune response; lung; microarray; oxygen transport.


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