Gene expression profile in response to potassium dichromate-induced toxicity in human dermal fibroblasts.
Joseph P; Umbright C; He Q
Toxicologist 2007 Mar; 96(1):132
Several adverse health effects including irritant and allergic contact dermatitis have been reported among workers following occupational exposure to chromium containing compounds. To understand the molecular mechanisms responsible for the dermal toxicity of chromium, a differential gene expression profile of human skin fibroblasts exposed to a cytotoxic concentration of hexavalent potassium dichromate [Cr(VI)] was studied. Skin fibroblasts were exposed to 5 micromolar Cr(VI) for time intervals up to 24-hours and a differential gene expression profile was studied using the human Toxicology and Drug Resistance Microarray (Super Array Inc.). Of the 280 genes represented on the array, 32 were found differentially expressed in the fibroblasts exposed to Cr(VI). In general, genes involved in stress response, cell cycle control, drug metabolism, apoptosis and growth were found differentially expressed in the Cr(VI) exposed fibroblasts. The molecular mechanisms responsible for the Cr(VI)-induced differential gene expression were investigated using heme oxygenase 1 (HO-1) as the model gene. HO-1 gene expression was significantly higher in the Cr(VI) exposed cells compared with the control cells. Preexposure of dermal fibroblasts to actinomycin D (inhibitor of transcription) and Nacetyl cysteine (scavenger of reactive oxygen species) blocked the Cr(VI)-induced overexpression of the HO-1 gene. Similarly, modulating the intracellular glutathione level by pre-treating cells with either BSO or glutathione significantly influenced the potential of Cr(VI) to induce the expression of the HO-1 gene. Similar results were obtained when experiments were conducted using a luciferase reporter gene expression system containing the HO-1 gene promoter. In conclusion, our results demonstrate that the cellular glutathione level may be an important determining factor in the dermal toxicity induced by hexavalent chromium.
Biodynamics; Chemical-reactions; Cell-biology; Cell-damage; Cell-metabolism; Cell-transformation; Cellular-reactions; Cell-cultures; Cell-function; Cell-morphology; Skin-disorders; Skin-exposure; Skin-irritants; Skin-sensitivity; Skin-tests; Dermatitis; Dermatosis; Irritants; Contact-allergies; Genetic-disorders; Humans
The Toxicologist. Society of Toxicology 46th Annual Meeting and ToxExpo, March 25-29, 2007, Charlotte, North Carolina