Changes in gene expression profiles of human fibroblasts in response to sodium arsenite treatment

Abstract

Arsenic compounds are widely distributed and arsenic ingestion is associated with many human diseases, including blackfoot disease, atherosclerosis, and cancers. However, the underlying mechanism of arsenic toxicity is not understood. In human fibroblast cells (HFW), arsenite is known to induce oxidative damage, chromosome aberrations, cell cycle arrest, and aneuploidy, and the manifestation of these cellular responses is dependent on changes in gene expression which can be analyzed using the cDNA microarray technique. In this study, cDNA microarray membranes with 568 human genes were used to examine mRNA profile changes in HFW cells treated for 0 to 24 h with 5 μM sodium arsenite. On the basis of the mean value for three independent experiments, 133 target genes were selected for a 2 × 3 self-organizing map cluster analysis; 94 were found to be induced by arsenite treatment, whereas 39 were repressed. These genes were categorized as signal transduction, transcriptional regulation, cell cycle control, stress responses, proteolytic enzymes, and miscellaneous. Significant changes in the signaling-related and transcriptional regulation genes indicated that arsenite induces complex toxicopathological injury.