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Global Gene Expression Profiling of Hyperkeratotic Skin Lesions from Inner Mongolians Chronically Exposed to Arsenic
Citation:
BAILEY, K., Y. Xia, W. O. WARD, J. MO, J. S. MUMFORD, R. D. OWEN, AND S. Y. THAI. Global Gene Expression Profiling of Hyperkeratotic Skin Lesions from Inner Mongolians Chronically Exposed to Arsenic. Journal of Toxicologic Pathology. The Japanese Society of Toxicologic Pathology, TOKYO, Japan, 37(7):849-859, (2009).
Impact/Purpose:
Hyperkeratosis is commonly the first lesion after exposure to arsenic in drinking water. The mechanism behind the formation of hyperkeratosis, and how they may ultimately progress to non-melanoma skin cancer is unknown. This study is to get insight into the transcriptional changes and in hyperkatosis skin tissue. From that, we can get more understanding of the signaling pathway changes that may lead to formation of hyperkeratosis and eventually some indication of the signaling pathway changes that may lead to skin cancer.
Description:
The skin is an organ that is highly sensitive to chronic arsenic exposure. Skin lesions such as hyperkeratoses (HKs), which are characterized by hyperproliferation and aberrations in terminal epidermal differentiation, are common early manifestations of arsenicosis in humans. HKs can be precursor lesions of non-melanoma skin cancers (NMSCs), but the driving forces behind their formation and how they may ultimately progress to NMSCs are unknown. The goal of this study was examine the global gene expression profiles of arsenic-related HKs in an effort to better understand gene expression changes that are potentially associated with early stages of arsenic carcinogenesis. HK biopsies were removed from individuals living in an arsenicosis-endemic region in Inner Mongolia who had been exposed to high levels of arsenic (212-950 ppb) in their drinking water for ≥ 20 years and exhibited skin changes commonly associated with chronic arsenic exposure. RNA was isolated from 7 HKs in this group and from 4 lesion-free skin samples from healthy individuals who live in a nearby area and who had been exposed to low lifetime arsenic levels (~7 ppb) in their drinking water. Gene expression profiling was performed on RNA from the two groups using Affymetrix® Human U133 Plus 2.0 arrays that contain 54,675 probe sets. Approximately 39% of transcripts recognized by these probe sets were expressed in all samples, and 2824 of these transcripts were differentially expressed between the two groups. Consistent with the pathological characteristics of the HK lesions, major categories of altered transcripts and known canonical pathways include those involved in development, differentiation, apoptosis, proliferation and stress response. The results of this study may help define a signature profile of gene expression changes associated with long-term arsenic exposure in the skin.
