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. 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

Angeline S Andrew  1 , David A Jewell, Rebecca A Mason, Michael L Whitfield, Jason H Moore, Margaret R Karagas
Affiliations

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

Angeline S Andrew et al. Environ Health Perspect. 2008 Apr.

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.

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Figures

Figure 1
Figure 1
Heat map of genes with statistically significant expression differences by arsenic exposure level. The rows represent the genes selected by SAM analysis. The heat-map colors depict the gene expression level from low (black) to high (red). Each column represents an individual (numbered at the bottom) with either high (dark gray bar at the bottom) or low (light gray) arsenic exposure level. Genes and individuals were hierarchically clustered by expression level.
Figure 2
Figure 2
Pathway Studio diagram of common regulators of differentially expressed genes. Genes with statistically significant expression differences were queried against the Pathway Studio ResNet 5.0 database to identify common regulators. Biological relationships are represented by red arrows for positive effects and green arrows for negative effects. Genes are represented by colored shapes: those with increased expression with high arsenic exposure are shown in red; those with decreased expression in response to high arsenic exposure are shown in green. Other genes that are directly involved in the pathway, but were not significantly modified at the gene expression level by arsenic exposure status, are shown in gray.
Figure 3
Figure 3
RT-PCR analysis of gene expression in relation to urinary arsenic (As). The graphs depict the normalized RT-PCR gene expression versus creatinine-normalized urinary arsenic exposure levels. (A) PRF1 (r2 = 0.2). (B) IL2RB (r2 = 0.3). (C) HLA-DRB1 (r2 = 0.8). (D) KIR3DL1 (r2 = 0.1).
See this image and copyright information in PMC

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