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

Abstract

BackgroundArsenic 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 μg/L in the northeastern, western, and north central regions of the United States.ObjectivesWe investigated the effects of arsenic exposure, defined by internal biomarkers at levels relevant to the United States and similarly exposed populations, on gene expression.MethodsWe 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.ResultsThe 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.ConclusionsThese 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.

Effects of spirulina in arsenic poisoning in the Black Bengal goat

“…Supplementation of spirulina to arsenic-treated goats did not significantly modify the IgG-positive to IgG-negative lymphocyte ratio or the IgM-positive lymphocytes in the lymph node. Arsenic has been recognized as a powerful immunomodulatory agent in many laboratory animals and in epidemiological studies (18). However, the insignificant effect of spirulina on immune functions in the present study might be due, in part, to large intake of green grass, which might provide more micronutrients and antioxidants than the small amount of spirulina.…”

Microarrays and Epidemiology: Ensuring the Impact and Accessibility of Research Findings

“…These studies have the potential to yield important insights about mechanisms of carcinogenesis. For example, Russo et al (9) reported a genomic signature associated with parity status in histologically normal breast tissue and Andrew et al (10) presented a lymphocyte gene expression signature associated with high versus low exposure to drinking water arsenic. Webb et al (2007) identified several challenges and limitations associated with matching and restriction for confounding control in microarray analyses, but an approach that has received surprisingly little attention is application of statistical methods.…”

Arsenic Induces Polyadenylation of Canonical Histone mRNA by Down-regulating Stem-Loop-binding Protein Gene Expression

“…Exposure to a carcinogenic metal, such as arsenic, has been associated with altered gene expression patterns both in vitro and in vivo, and it has been demonstrated that the arsenicinduced changes in gene expression may be epigenetically regulated (2)(3)(4)(5)(6)(7)(8)(9). Although arsenic is capable of inducing changes in gene expression by altering the levels of post-translational histone modifications in the promoters of genes, alterations in the expression of the histone genes themselves by arsenic has not been studied.…”