Effects of the Lung Carcinogen Silica on Cyclooxygenase-2 and Prostaglandin E2 Expression in RAW 264.7 Cells

Details

• Personal Author:
  Harris GK ; Shi X ; Zhang Z
• Description:
  Silica is a mineral which is associated with a number of lung diseases, including lung cancer, mesothelioma and silicosis. Elevated levels of the proteins Cyclooxygenase-2 (Cox-2) and Prostaglandin E2 (PGE2) synthase have been observed in lung cancer in a number of in vitro and in vivo studies. Few studies have examined the link between silica exposure and the expression of Cox-2 and PGE2 synthase, however. The purpose of this study was to investigate the effects of silica on Cox-2 and PGE2 synthase expression in RAW 264.7 mouse macrophage cells. RAW cells were incubated with silica at 0, 10, 50, 100 or 1,000 microg/ml for 12 hours. As a positive control for Cox-2 expression, lipopolysaccharide (LPS) was administered for 12 hours to a 6th treatment group at 10 microg/ml. Silica treatment induced Cox-2 and PGE2 protein expression in a dose-dependent manner. The highest dose silica-treated group induced Cox-2 to a greater degree, than did the LPS positive control. Based on previous studies in our laboratory which indicated that silica affects signal transduction pathways upstream of Cox-2, particularly those associated with MAP Kinase pathways, further studies were conducted using specific inhibitors. Using the highest (1,000 microg/ml silica dose, the inhibitors SB 203580 (a p38 MAP Kinase Inhibitor), PD 98059 (a MEK1 Inhibitor for ERK), UO126 (an ERK inhibitor), Calpain Inhibitor I (an NFkB Inhibitor), and Cannabinol (a CREB/ATF:1 Inhibitor) were tested for their effects on Cox-2 expression. Only SB 203580 attenuated Cox-2 protein expression. The results of this study indicate that silica exposure induces both Cox-2 and PGE2 expression and that silica-induced Cox-2 expression is partially dependent on p38 MAP Kinase. [Description provided by NIOSH]
• Subjects:
  Carcinogens Cells, Cultured Lung Lung Diseases Neoplasms Occupational Health Respiratory System Respiratory Tract Diseases Safety Silicon Dioxide
• Keywords:
  Cancer Cell-alteration Cell-cultures Cell-damage Cellular-reactions Dose-response In-vitro-study Lung-cancer Mesothelial-cells Prostaglandin-inhibitors Protein-synthesis Proteins Silica-dusts Silicosis

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• ISSN:
  0197-016X
• Publisher:
  American Association for Cancer Research
• Document Type:
  Text
• Genre:
  Abstract or Summary ; Proceedings
• Place as Subject:
  California ; OSHA Region 3 ; OSHA Region 9 ; 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:
  43
• NIOSHTIC Number:
  nn:20033745
• Citation:
  Proceedings of the 93rd American Association for Cancer Research Annual Meeting, April 6-10, 2002, San Francisco, California. Philadelphia, PA: American Association for Cancer Research, 2002 Apr; 43:470
• CAS Registry Number:
  Quartz (SiO2) (CAS RN 14808-60-7)
• Federal Fiscal Year:
  2002
• NORA Priority Area:
  Research Tools and Approaches: Cancer Research Methods
• Peer Reviewed:
  False
• Source Full Name:
  Proceedings of the 93rd American Association for Cancer Research Annual Meeting, April 6-10, 2002, San Francisco, California
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:6596c3cd58c514d87b748aa3f79e5762167af71d0a697b2ea08608efaf4e3971c1b886e236e52909969c531b34c00d4502effc15830023825ebbb9139482cbcc
• Download URL:
  https://stacks.cdc.gov/view/cdc/189202/cdc_189202_DS1.pdf
• File Type:
  [PDF - 366.40 KB ]