Document Detail

Ambient particulate matter causes activation of the c-jun kinase/stress-activated protein kinase cascade and DNA synthesis in lung epithelial cells.
MedLine Citation:
PMID:  9788597     Owner:  NLM     Status:  MEDLINE    
Numerous epidemiological studies have demonstrated a positive association between ambient air pollution and adverse health effects including respiratory morbidity, asthma, and lung cancer. It has been suggested in some experimental studies that airborne particulate matter (PM) can produce inflammatory effects, but nothing is known about the possible proliferative and carcinogenic effects of these particles on cells of the lung. We show here that exposure of pulmonary epithelial cells, a cell type affected in acute lung injury, asthma, and lung carcinomas, to nontoxic concentrations of PM in vitro results in increases in c-jun kinase activity, levels of phosphorylated cJun immunoreactive protein, and transcriptional activation of activator protein-1-dependent gene expression. These changes are accompanied by elevations in numbers of cells incorporating 5'-bromodeoxyuridine, a marker of unscheduled DNA synthesis and/or cell proliferation. Data here are the first to demonstrate that interaction of ambient PM with target cells of the lung initiates a cell signaling cascade related causally to aberrant cell proliferation and carcinogenesis.
C Timblin; K BeruBe; A Churg; K Driscoll; T Gordon; D Hemenway; E Walsh; A B Cummins; P Vacek; B Mossman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cancer research     Volume:  58     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  1998 Oct 
Date Detail:
Created Date:  1998-11-06     Completed Date:  1998-11-06     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  4543-7     Citation Subset:  IM    
Department of Pathology, University of Vermont, Burlington 05405, USA.
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MeSH Terms
Air Pollution / adverse effects*
Bromodeoxyuridine / metabolism
Calcium-Calmodulin-Dependent Protein Kinases / physiology*
Cell Division
DNA / biosynthesis*
Enzyme Activation
Epithelial Cells / metabolism
JNK Mitogen-Activated Protein Kinases
Lung / metabolism*
Mitogen-Activated Protein Kinases*
Transcription Factor AP-1 / physiology
Grant Support
Reg. No./Substance:
0/Transcription Factor AP-1; 59-14-3/Bromodeoxyuridine; 9007-49-2/DNA; EC Protein Kinases; EC Mitogen-Activated Protein Kinases; EC Protein Kinases

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