Heme-Oxygenase 1 Gene Expression Is a Marker for Hexavalent Chromium-Induced Stress and Toxicity in Human Dermal Fibrosis

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 who are occupationally exposed to chromium-containing compounds. Human dermal fibroblasts were used as an in vitro experimental model to study the potential mechanisms underlying hexavalent chromium [Cr(VI)]-induced dermal toxicity. Exposure of the fibroblasts to 5microM Cr(VI) (LC50 for a 24-h exposure period) followed by microarray analysis of the gene expression profile revealed overexpression of several genes including those involved in cell stress response. The cellular level of glutathione, the major antioxidant molecule present in the cells, was significantly lower in the Cr(VI)-treated cells compared to the corresponding control cells. The Cr(VI)-induced overexpression of heme-oxygenase 1 messenger RNA (HO-1) in the fibroblasts was significantly blocked by actinomycin D and by inhibitors of MAP kinase pathways. The Cr(VI)-induced cytotoxicity and the overexpression of the HO-1 gene were dependent on the glutathione level of the fibroblasts. Buthionine sulfoximine-mediated GSH depletion resulted in enhanced Cr(VI) cytotoxicity and further overexpression of the HO-1 gene. On the other hand, elevated cellular levels of glutathione resulting from pretreating the cells with GSH significantly protected the cells against the Cr(VI)-induced cytotoxicity and blocked the HO-1 gene's overexpression. Pretreating the fibroblasts with N-acetyl cysteine also significantly reduced the Cr(VI)-induced cytotoxicity and overexpression of the HO-1 gene. In conclusion, depletion of GSH leading to cellular stress is a major mechanism responsible for Cr(VI)-induced cytotoxicity. Furthermore, the expression level of HO-1 gene is a marker for Cr(VI)-induced cell stress leading to cytotoxicity. [Description provided by NIOSH]
• Subjects:
  Chemistry Chromium Cytotoxins Dermatitis Hypersensitivity Occupational Exposure Occupational Health Safety Skin Skin Diseases Welding

  More +
• Keywords:
  Allergic-dermatitis Cell-damage Chemical-hypersensitivity Chemical-properties Chrome-plating Chromium-compounds Contact-allergies Contact-dermatitis Cytotoxic-effects Occupational-exposure Welding-industry

  More +
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  California ; Maryland ; OSHA Region 3 ; OSHA Region 9 ; Virginia ; 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:
  325-334
• Volume:
  103
• Issue:
  2
• NIOSHTIC Number:
  nn:20033837
• Citation:
  Toxicol Sci 2008 Jun; 103(2):325-334
• Contact Point Address:
  Pius Joseph, MS 3014, Molecular Carcinogenesis Laboratory, Toxicology and Molecular Biology Branch, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505
• Email:
  pjoseph1@cdc.gov
• CAS Registry Number:
  Chromium(6+) (CAS RN 18540-29-9)
• Federal Fiscal Year:
  2008
• Peer Reviewed:
  True
• Source Full Name:
  Toxicological Sciences
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:c592addef022a9361e5d336a203832a4f6fc0f4281c7110977513ba958cc4baed478dd1e391deda281bbc160c50b0a7596b0363d09c394ef0a4875002287ee37
• Download URL:
  https://stacks.cdc.gov/view/cdc/189261/cdc_189261_DS1.pdf
• File Type:
  [PDF - 328.76 KB ]