Drinking-Water Arsenic Exposure Modulates Gene Expression in Human Lymphocytes from a U.S. Population Angeline S. Andrew,1 David A. Jewell,2 Rebecca A. Mason,1 Michael L. Whitfield,2 Jason H. Moore,2 and Margaret R. Karagas1 1Department of Community and Family Medicine, Section of Biostatistics and Epidemiology, and 2Department of Genetics, Dartmouth Medical School, Lebanon, New Hampshire, USA Abstract 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) as part of a case–control study in New Hampshire were selected based on high- versus low-level arsenic exposure levels. Results: The biologic functions of the transcripts that showed statistically significant abundance differences between high- and low-arsenic exposure groups included an overrepresentation of genes involved in defense response, immune function, cell growth, apoptosis, regulation of cell cycle, T-cell receptor signaling pathway, and diabetes. Notably, the high-arsenic exposure group exhibited higher levels of several killer cell immunoglobulin-like receptors that inhibit natural killer cell activity. Conclusions: These findings define biologic changes that occur with chronic arsenic exposure in humans and provide leads and potential targets for understanding and monitoring the pathogenesis of arsenic-induced diseases. Key words: arsenic, drinking water, immune response, lymphocytes, microarray, U.S. population. Environ Health Perspect 116:524–531 (2008) . doi:10.1289/ehp.10861 available via http://dx.doi.org/ [Online 23 January 2008]] Address correspondence to A.S. Andrew, Dartmouth Medical School Section of Biostatistics and Epidemiology, 7927 Rubin 860, One Medical Center Dr., Lebanon, NH 03756 USA. Telephone: (603) 653-9019. Fax: (603) 653-9093. E-mail: Angeline.Andrew@dartmouth.edu Supplemental Material is available online at http://www.ehponline.org/members/2008/10899/suppl.pdf Funding was provided by the National Institutes of Health (NIH) : K07 CA102327, R03 CA121382, R03 CA99500, and R01CA57494 [National Cancer Institute (NCI) ] ; P20 RR018787 (National Center for Research Resources IDeA program) ; and P42 ES07373 [National Institute of Environmental Health Sciences (NIEHS) and the Dartmouth Superfund Basic Research Program]. Contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the NIEHS, NCI, or NIH. The authors declare they have no competing financial interests. Received 6 September 2007 ; accepted 21 January 2008. The full version of this article is available for free in HTML or PDF formats. |