Asbestos Induces Activator Protein-1 Transactivation in Transgenic Mice

Details

• Personal Author:
  Castranova, Vincent ; Chen F ; Ding M ; Dong Z ; Ma W ; Pack D ; Shi X ; Vallyathan V ; Ye J
• Description:
  Activation of activator protein (AP-1) by crocidolite asbestos was examined in vitro in a JB6 P+ cell line stably transfected with AP-1-luciferase reporter plasmid and in vivo using AP-1-luciferase reporter transgenic mice. In in vitro studies, crocidolite asbestos caused a dose- and time-dependent induction of AP-1 activation in cultured JB6 cells. The elevated AP-1 activity persisted for at least 48 h. Crocidolite asbestos also induced AP-1 transactivation in the pulmonary and bronchial tissues of transgenic mice. AP-1 activation was observed at 2 days after intratracheal instillation of the mice with asbestos. At 3 days postexposure, AP-1 activation was elevated 10-fold in the lung tissue and 22-fold in bronchiolar tissue as compared with their controls. The induction of AP-1 activity by asbestos appeared to be mediated through the activation of mitogen-activated protein kinase family members, including extracellular signal-regulating protein kinase, Erk1 and Erk2. Aspirin inhibited asbestos-induced AP-1 activity in JB6 cells. Pretreatment of the mice with aspirin also inhibited asbestos-induced AP-1 activation in bronchiolar tissue. The data suggest that further investigation of the role of AP-1 activation in asbestos-induced cell proliferation and carcinogenesis is warranted. In addition, investigation of the potential therapeutic benefits of aspirin in the prevention/amelioration of asbestos-induced cancer is justified. [Description provided by NIOSH]
• Subjects:
  Animals Lung Lung Diseases Neoplasms Occupational Health Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Animal-studies Bronchial-cancer Carcinomas In-vitro-studies In-vivo-studies Mesothelial-cells Pulmonary-cancer Pulmonary-system-disorders
• ISSN:
  0008-5472
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Minnesota ; OSHA Region 3 ; OSHA Region 5 ; 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:
  59
• Issue:
  8
• NIOSHTIC Number:
  nn:20000967
• Citation:
  Cancer Res 1999 Apr; 59(8):1884-1889
• CAS Registry Number:
  Uranate(4-), dioxotriperoxy-, lithium (1:4), (HB-8-22-111′1′1′′1′′)- (CAS RN 12201-28-4)
• Federal Fiscal Year:
  1999
• Peer Reviewed:
  True
• Source Full Name:
  Cancer Research
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:5148b2c37cf1f7c7dc7f53d21f2663e855b123b669c4943dfe60f7bfc93ce119ac9fcbd8792785b08e4540b272af00be545540554632e2e621391cbccaf2df1f
• Download URL:
  https://stacks.cdc.gov/view/cdc/198279/cdc_198279_DS1.pdf
• File Type:
  [PDF - 1.49 MB ]