Journal of Carcinogenesis & Mutagenesis

Abstract

Transcriptomics Evaluation of Hexavalent Chromium Toxicity in Human Dermal Fibroblasts

Rajendran Sellamuthu, Christina Umbright, Rebecca Chapman, Stephen Leonard, Shengqiao Li, Michael Kashon and Pius Joseph

Significant exposure to hexavalent chromium, a metal with broad toxicity potential in humans, has been reported. In order to understand the mechanisms of dermal toxicity induced by hexavalent chromium, global gene expression profiling of human dermal fibroblasts exposed to potassium dichromate was performed. Microarray analysis of the gene expression profile in the fibroblasts treated with potassium dichromate identified significant differential expression of approximately 1,200 transcripts compared with the control cells. Functional categorization of the differentially expressed genes identified the enrichment of genes involved in several cellular processes, including apoptosis and oxidative stress, in the fibroblasts exposed to hexavalent chromium. Induction of apoptosis and oxidative stress in the dermal fibroblasts in response to their exposure to chromium was independently confirmed by additional experiments. The potassium dichromate-induced cytotoxicity, apoptosis, and oxidative stress were significantly blocked by the addition of ferrous sulfate, an agent known for its ability to reduce chromium to the insoluble and therefore impermeable trivalent form, to the cell culture medium. Taken together, our data provide insights into the potential mechanisms underlying the dermal toxicity of hexavalent chromium and provide experimental support for the proposed protective role of ferrous sulfate in hexavalent chromium-induced toxicity.