Drinking-Water Arsenic Exposure Modulates Gene Expression in Human Lymphocytes from a U.S. Population

• Published in: Environmental health perspectives 2008-04, Vol.116 (4), p.524-531
• Main Authors: Andrew, Angeline S., Jewell, David A., Mason, Rebecca A., Whitfield, Michael L., Moore, Jason H., Karagas, Margaret R.
• Format: Article
• Language: English
• Subjects: Aged; Arsenic; Arsenic - toxicity; Blood; Cancer; Complications and side effects; Diabetes; Dose-Response Relationship, Drug; Environmental Exposure - adverse effects; Environmental health; Female; Gene expression; Gene Expression - drug effects; Genes; Humans; Lymphocytes; Lymphocytes - metabolism; Male; Natural killer cells; Oligonucleotide Array Sequence Analysis; Receptors; Risk factors; T lymphocytes; United States; Water Pollutants, Chemical - toxicity; Water Supply
• ISSN: 0091-6765; 1552-9924
• DOI: 10.1289/ehp.10861

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 micrograms/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.