Gene expression profile in human skin fibroblasts exposed to potassium dichromate.
Toxicologist 2006 Mar; 90(1):240
Chromium containing compounds are extensively used in various applications resulting in significant human exposure. Several adverse health effects, including irritant and allergic contact dermatitis, have been reported among workers following occupational exposure to chromium containing compounds. In order to better understand the molecular mechanisms responsible for the dermal toxicity of chromium, differential gene expression profiles of human skin fibroblasts exposed to a cytotoxic concentration of hexavalent potassium dichromate [Cr(VI)] were studied. Skin fibroblasts were exposed to 5 uM Cr(VI) for time intervals up to 24- hr and their differential gene expression profile was studied using the Toxicology and Drug Resistance Microarray (Super Array Inc.). Of the 280 genes represented on the array, the expression levels of 32 genes were found to be differentially affected in the fibroblasts exposed to Cr(VI). In general, genes involved in stress response, cell cycle control, drug metabolism, apoptosis and growth were differentially expressed in response to Cr(VI) exposure. The role of intracellular glutathione on the Cr(VI)-induced alterations in the expression of genes was further investigated using heme oxygenase 1 (HO-1) as the model gene. Modulating the intracellular glutathione level by pre-treating the cells with either BSO (buthionine- Sulfoximine) or glutathione significantly influenced the potential of Cr(VI) to induce expression of the HO-1 gene. Pre-treating the cells with BSO resulted in a significant reduction in glutathione levels. The Cr-induced overexpression of the HO-1 gene in the BSO-treated cells was significantly higher than in those cells without BSO treatment. On the other hand, pre-treating the cells with glutathione partially blocked the Cr(VI)-induced overexpression of the HO-1 gene. In conclusion, our results demonstrate that Cr(VI) exerts its toxic effects in human skin fibroblasts by multiple mechanisms involved in various cellular functions; and the cellular glutathione level appears to be an important factor influencing Cr(VI)'s effects on the expression of genes.
Skin; Potassium-compounds; Chromium-compounds; Allergic-dermatitis; Dermatitis; Dermatology; Dermatosis; Skin-diseases; Skin-irritants; Occupational-exposure; Cytotoxins; Cytotoxicity; Cytotoxic-effects; Exposure-levels; Exposure-assessment; Toxins; Toxic-effects
Research Tools and Approaches: Cancer Research Methods
The Toxicologist. Society of Toxicology 45th Annual Meeting and ToxExpo, March 5-9, 2006, San Diego, California