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


OBJECTIVE
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.
Andrew
Angeline S
AS
Dartmouth Medical School Section of Biostatistics and Epidemiology, 7927 Rubin 860, One Medical Center Dr., Lebanon, NH 03756, USA. Angeline.Andrew@dartmouth.edu
Jewell
David A
DA
Mason
Rebecca A
RA
Whitfield
Michael L
ML
Moore
Jason H
JH
Karagas
Margaret R
MR
D000368:Aged; D001151:Arsenic / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D014481:United States; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D014881:Water Supply
D014874:Water Pollutants, Chemical; D001151:Arsenic