Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population

Environ Health Perspect. 2008 Apr;116(4):524-31. 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 microg/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.

Keywords: U.S. population; arsenic; drinking water; immune response; lymphocytes; microarray.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Arsenic / toxicity*
  • Dose-Response Relationship, Drug
  • Environmental Exposure / adverse effects*
  • Female
  • Gene Expression / drug effects*
  • Humans
  • Lymphocytes / metabolism
  • Male
  • Oligonucleotide Array Sequence Analysis
  • United States
  • Water Pollutants, Chemical / toxicity*
  • Water Supply*


  • Water Pollutants, Chemical
  • Arsenic