Gene Expression Profile in Response to Potassium Dichromate-Induced Toxicity in Human Dermal Fibroblasts

Details

• Personal Author:
  He Q ; Joseph P ; Umbright C
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Cells, Cultured Chemistry Dermatitis Genetics Hypersensitivity Irritants Occupational Health Safety Skin Skin Diseases
• Keywords:
  Biodynamics Cell-biology Cell-cultures Cell-damage Cell-function Cell-metabolism Cell-morphology Cell-transformation Cellular-reactions Chemical-reactions Contact-allergies Dermatosis Genetic-disorders Humans Skin-disorders Skin-exposure Skin-irritants Skin-sensitivity Skin-tests

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  132
• Volume:
  96
• Issue:
  1
• NIOSHTIC Number:
  nn:20031913
• Citation:
  Toxicologist 2007 Mar; 96(1):132
• Federal Fiscal Year:
  2007
• Peer Reviewed:
  False
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:6538427d181e30582205b59d63073ece1f5efabaef5c6a9c5d2ab325c83d5857b9fb0e8ced03bcdd0089898a440325558ecfd529fedcc2f2bf1f29910d67689d
• Download URL:
  https://stacks.cdc.gov/view/cdc/186024/cdc_186024_DS1.pdf
• File Type:
  [PDF - 518.02 KB ]