期刊
TOXICOLOGY LETTERS
卷 169, 期 2, 页码 162-176出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2007.01.006
关键词
selenium; gene expression; micro-array; arsenic; skin lesion
类别
资金
- NCI NIH HHS [R01 CA102484, R01 CA107431] Funding Source: Medline
- NIEHS NIH HHS [P42 ES010349, P42 ES10349, P30 ES09089, P30 ES009089] Funding Source: Medline
The molecular basis and downstream targets of oral selenium supplementation in individuals with elevated risk of cancer due to chronic exposure from environmental carcinogens has been largely unexplored. In this study, we investigated genome-wide differential gene expression in peripheral blood mononuclear cells (PBMC) from individuals with pre- malignant arsenic (As)-induced skin lesions before and after 6 months daily oral supplementation of 200 mu g L-selenomethionine. The Affymetrix GeneChip Human 133A 2.0 array, containing probes for 22,277 gene transcripts, was used to assess gene expression. Three different normalization methods, RMA (robust multi-chip analysis), GC-RMA and PLIER (Probe logarithmic intensity error), were applied to explore differentially expressed genes. We identified a list of 28 biologically meaningful, significantly differentially expressed genes. Genes up-regulated by selenium supplementation included TNF, IL1B, IL8, SOD2, CXCL2 and several other immunological and oxidative stress-related genes. When mapped to a biological association network, many of the differentially expressed genes were found to regulate functional classes such as fibroblast growth factor, collagenase, matrix metalloproteinase and stromelysin-1, and thus, considered to affect cellular processes like apoptosis, proliferation and others. Many of the significantly up-regulated genes following selenium-supplementation were previously found by us to be down-regulated in a different set of individuals with As-induced skin lesions compared to those without. In conclusion, findings from this study may elucidate the biological effect of selenium supplementation in humans. Additionally, this study suggests that long-term selenium supplementation may revert some of the gene expression changes presumably induced by chronic As exposure in individuals with pre-malignant skin lesions. (c) 2007 Elsevier Ireland Ltd. All rights reserved.
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