Pro/Antioxidant Status in Murine Skin Following Topical Exposure to Cumene Hydroperoxide Throughout the Ontogeny of Skin Cancer

Details

• Personal Author:
  Castranova, Vincent ; Kisin ER ; Kommineni C ; Murray A ; Shvedova AA ; Vallyathan V
• Description:
  Organic peroxides used in the chemical and pharmaceutical industries have a reputation for being potent skin tumor promoters and inducers of epidermal hyperplasia. Their ability to trigger free radical generation is critical for their carcinogenic properties. Short-term in vivo exposure of mouse skin to cumene hydroperoxide (Cum-OOH) causes severe oxidative stress and formation of spin-trapped radical adducts. The present study was designed to determine the effectiveness of Cum-OOH compared to 12-O-tetradecanoylphorbol-13-acetate (TPA) in the induction of tumor promotion in the mouse skin, to identify the involvement of cyclooxygenase-2 (COX-2) in oxidative metabolism of Cum-OOH in keratinocytes, and to evaluate morphological changes and outcomes of oxidative stress in skin of SENCAR mice throughout a two-stage carcinogenesis protocol. Dimethyl-benz[a]anthracene (DMBA)-initiated mice were treated with Cum-OOH (32.8 µmol) or TPA (8.5 nmol) twice weekly for 20 weeks to promote papilloma formation. Skin carcinoma formed only in DMBA/Cum-OOH-exposed mice. Higher levels of oxidative stress and inflammation (as indicated by the accumulation of peroxidative products, antioxidant depletion, and edema formation) were evident in the DMBA/Cum-OOH group compared to DMBA/TPA treated mice. Exposure of keratinocytes (HaCaT) to Cum-OOH for 18 h resulted in expression of COX-2 and increased levels of PGE2. Inhibitors of COX-2 efficiently suppressed oxidative stress and enzyme expression in the cells treated with Cum-OOH. These results suggest that COX-2-dependent oxidative metabolism is at least partially involved in Cum-OOH-induced inflammatory responses and thus tumor promotion. [Description provided by NIOSH]
• Subjects:
  Antioxidants Biopharmaceutics Neoplasms Nitrogen Compounds Nitrogen Oxides Occupational Health Peroxides Pharmacies Safety Skin Skin Diseases

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• Keywords:
  12-O-tetradecanoylphorbol-13-acetate Author Keywords: Cumene Hydroperoxide Diseases Exposure-levels Nitrogen-compounds Nitrogen-oxides Oxidative Stress Pharmaceutical-industry Pharmaceuticals Skin Skin-cancer Skin-diseases Skin-disorders Skin-tumors Tumor Promotion

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• ISSN:
  0006-2979
• Document Type:
  Text
• Genre:
  Journal Article
• 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:
  23-31
• Volume:
  69
• Issue:
  1
• NIOSHTIC Number:
  nn:20024385
• Citation:
  Biochemistry 2004 Jan; 69(1):23-31
• Contact Point Address:
  Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, 1095 Willowdale Road, M/S 2015, Morgantown, West Virginia, USA
• Email:
  ats1@cdc.gov
• CAS Registry Number:
  Cumene hydroperoxide (CAS RN 80-15-9) ; Hydrogen peroxide (CAS RN 7722-84-1)
• Federal Fiscal Year:
  2004
• NORA Priority Area:
  Disease and Injury: Allergic and Irritant Dermatitis
• Peer Reviewed:
  True
• Source Full Name:
  Biochemistry
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:7fefa77b3da3780c8be12f608bf62efbde54672e7676c0f7c42ae4ef7463af394475ee135df63dc90034a03465ab21a278ee221cd6c7a77903454d6e07e491a9
• Download URL:
  https://stacks.cdc.gov/view/cdc/196211/cdc_196211_DS1.pdf
• File Type:
  [PDF - 129.54 KB ]