Abstract
BackgroundArsenic is a carcinogen that is known to induce cell transformation and tumor formation. Although studies have been performed to examine the modulation of signaling molecules caused by arsenic exposure, the molecular mechanisms by which arsenic causes cancer are still unclear. We hypothesized that arsenic alters gene expression leading to carcinogenesis in the lung.ResultsIn this study, we examined global gene expression in response to 0.75 μM arsenic treatment for 1–7 days in a rat lung epithelial cell line (L2) using an in-house 10 k rat DNA microarray. One hundred thirty one genes were identified using the one-class statistical analysis of microarray (SAM) test. Of them, 33 genes had a fold change of ≥ 2 between at least two time points. These genes were then clustered into 5 groups using K-means cluster analysis based on their expression patterns. Seven selected genes, all associated with cancer, were confirmed by real-time PCR. These genes have functions directly or indirectly related to metabolism, glycolysis, cell proliferation and differentiation, and regulation of transcription.ConclusionOur findings provide important insight for the future studies of arsenic-mediated lung cancer.
Highlights
Arsenic is a carcinogen that is known to induce cell transformation and tumor formation
In addition to activating kinases, arsenic is known to regulate transcription factors including AP-1 [18,19,20] and NFkB [21,22,23]. These findings strongly suggest that arsenic is involved in the disturbance of the regulation of these pathways, which may lead to cancer
When grown to 80 to 90% confluence, the cells were treated for 7 days with sodium arsenite (0–5 μM)
Summary
Arsenic is a carcinogen that is known to induce cell transformation and tumor formation. We hypothesized that arsenic alters gene expression leading to carcinogenesis in the lung. Arsenic is a carcinogen that causes lung cancer as well as skin, bladder and kidney cancers [1]. Several mechanisms for arsenic-induced carcinogenesis have been proposed including genetic and epigenetic changes, inhibition of DNA repair, oxidative stress, alterations in cell death and proliferation, and aberrant activation of signal transduction pathways [3]. Exposure of TM3 testicular Leydig cells to arsenic results in the changes in DNA methylation and mutations as determined by random amplified polymorphic DNA (RAPD) [4]. Arsenic exposure reduces DNA repair probably by inhibiting DNA (page number not for citation purposes)
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