Exposure to Asphalt Fumes Activates Activator Protein-1 Through the Phosphatidylinositol 3-Kinase/Akt Signaling Pathway in Mouse Epidermal Cells

Details

• Personal Author:
  Luo J ; Ma C ; Wang J
• Description:
  Occupational exposure to asphalt fumes may pose a health risk. Experimental studies using animal and in vitro models indicate that condensates from asphalt fumes are genotoxic and can promote skin tumorigenesis. Enhanced activity of activator protein-1 (AP-1) is frequently associated with the promotion of skin tumorigenesis. The current study investigated the effect of exposure to asphalt fumes on AP-1 activation in mouse JB6 P+ epidermal cells and the skin of transgenic mice expressing the AP-1 luciferase reporter gene. Asphalt fumes were generated from a dynamic generation system that simulated road-paving conditions. Exposure to asphalt fumes significantly increased AP-1 activity in JB6 P+ cells as well as in cultured keratinocytes isolated from transgenic mice expressing AP-1 reporter. In addition, topical application of asphalt fumes by painting the tail skin of mice increased AP-1 activity by 14-fold. Exposure to asphalt fumes promoted basal as well as epidermal growth factor-stimulated anchorage-independent growth of JB6 P+ cells in soft agar. It activated phosphatidylinositol 3-kinase and induced phosphorylation of Akt at Ser-473/Thr-308, and concurrently activated downstream p70 S6 kinase as well as glycogen synthase kinase-3. Asphalt fumes transiently activated c-Jun NH2-terminal kinases without affecting extracellular signal-regulated kinases and p38 mitogen-activated protein kinases. Further study indicated that blockage of phosphatidylinositol 3-kinase activation eliminated asphalt fume-stimulated AP-1 activation and formation of anchorage-independent colonies in soft agar. This is the first report showing that exposure to asphalt fumes can activate AP-1 and intracellular signaling that may promote skin tumorigenesis, thus providing important evidence on the potential involvement of exposure to asphalt fumes in skin carcinogenesis. [Description provided by NIOSH]
• Subjects:
  Animals Carcinogens Environmental Monitoring Genetics Hydrocarbons Laboratories Occupational Health Polycyclic Aromatic Hydrocarbons Safety Skin Skin Diseases

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• Keywords:
  Animal-studies Asphalt-fumes Carcinogenesis Cell-function Cellular-reactions Exposure-assessment Exposure-methods Genes Laboratory-animals Polycyclic-aromatic-hydrocarbons Proteins Skin-disorders Skin-exposure Skin-tumors Tumorigenesis

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• ISSN:
  0021-9258
• 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
• Volume:
  278
• Issue:
  45
• NIOSHTIC Number:
  nn:20032144
• Citation:
  J Biol Chem 2003 Nov; 278(45):44265-44272
• Contact Point Address:
  Department of Microbiology, Immunology, and Cell Biology, West Virginia University School of Medicine, Robert C. Byrd Health Science Center, Morgantown, WV 26506
• CAS Registry Number:
  Anthracene (CAS RN 120-12-7) ; Dichloromethane (CAS RN 75-09-2) ; Hexane (CAS RN 110-54-3)
• Federal Fiscal Year:
  2004
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Biological Chemistry
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:70e124514b3cee55182440a7ad1635c9c23bcca836d17c8993205320b22aea538ae938e34855e9054b2c3a7ac769b72dea08c747f9078b2556eeb9e4991c07cd
• Download URL:
  https://stacks.cdc.gov/view/cdc/186191/cdc_186191_DS1.pdf
• File Type:
  [PDF - 391.45 KB ]