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Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.

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

Author information

1
Dartmouth Medical School Section of Biostatistics and Epidemiology, 7927 Rubin 860, One Medical Center Dr., Lebanon, NH 03756, USA. Angeline.Andrew@dartmouth.edu

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 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

PMID:
18414638
PMCID:
PMC2290973
DOI:
10.1289/ehp.10861
[Indexed for MEDLINE]
Free PMC Article

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