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GENE EXPRESSION PROFILING OF HYPERKERATOTIC SKIN FROM INNER MONGOLIANS CHRONICALLY EXPOSED TO ARSENIC
Citation:
BAILEY, K., J. MO, S. Y. THAI, AND J. S. MUMFORD. GENE EXPRESSION PROFILING OF HYPERKERATOTIC SKIN FROM INNER MONGOLIANS CHRONICALLY EXPOSED TO ARSENIC. Presented at Society of Toxicology Annual Meeting 2007, Charlotte, NC, March 25 - 29, 2007.
Impact/Purpose:
These results suggest that arsenic-related gene expression changes in human samples are mechanistically consistent with previously observed laboratory studies of arsenic carcinogenesis and may identify useful biomarkers of arsenic exposure.
Description:
Millions of people worldwide have been chronically exposed to arsenic levels in drinking water that greatly exceed the current World Health Organization¿s recommended limit of 10 µg/ml. The skin is a major target of arsenic toxicity, and some of the first clinical signs of chronic arsenicosis are skin abnormalities including abnormal pigmentation and hyperkeratoses (HK), which pose a high risk for cancer development. The Bayingnormen (Ba Men) region of Inner Mongolia has over 300,000 residents that have been exposed to high levels of arsenic in the drinking water for >20 years. Many of these residents have clinical symptoms of chronic arsenic exposure. To further our understanding of the mechanisms of arsenic toxicity, we examined the gene expression of arsenic-exposure-related HK from 7 Ba Men individuals (exposed to 212-950 µg/ml arsenic in drinking water) and non-lesioned skin from 4 control subjects from a nearby area (exposed to 7 µg/ml arsenic in drinking water). Gene expression profiling using Affymetrix® GeneChip Human U133 Plus 2.0 arrays was performed on RNA isolated from these samples. Over 4000 genes had differential expression in HK compared to normal skin (1-way ANOVA, p≤0.05; ≥1.5-fold change in expression). The HK samples had keratin gene expression patterns characteristic of hyperproliferative skin. In addition, the altered genes in HK are consistent with proposed mechanisms of arsenic carcinogenesis. Genes that are altered in response to oxidative stress (HMOX-1, CAT, NQO1, GPX2), DNA damage (GADD45A, XPC, XRCC5, DDB2) and modulation of apoptosis and cell cycle were all changed in HK skin. These results suggest that arsenic-related gene expression changes in human samples are mechanistically consistent with previously observed laboratory studies of arsenic carcinogenesis and may identify useful biomarkers of arsenic exposure.