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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Heintz, N. H. Janssen, Y. M. Mossman, B. T. |
| Description | Author Affiliation: Heintz NH ( Department of Pathology, University of Vermont College of Medicine, Burlington 05405.); |
| Abstract | To investigate the mechanisms of asbestos-induced carcinogenesis, expression of c-fos and c-jun protooncogenes was examined in rat pleural mesothelial cells and hamster tracheal epithelial cells after exposure to crocidolite or chrysotile asbestos. In contrast to phorbol 12-myristate 13-acetate, which induces rapid and transient increases in c-fos and c-jun mRNA, asbestos causes 2- to 5-fold increases in c-fos and c-jun mRNA that persist for at least 24 hr in mesothelial cells. The induction of c-fos and c-jun mRNA by asbestos in mesothelial cells is dose-dependent and is most pronounced with crocidolite, the type of asbestos most pathogenic in the causation of pleural mesothelioma. Induction of c-jun gene expression by asbestos occurs in tracheal epithelial cells but is not accompanied by a corresponding induction of c-fos gene expression. In both cell types, asbestos induces increases in protein factors that bind specifically to the DNA sites that mediate gene expression by the AP-1 family of transcription factors. The persistent induction of AP-1 transcription factors by asbestos suggests a model of asbestos-induced carcinogenesis involving chronic stimulation of cell proliferation through activation of the early response gene pathway that includes c-jun and/or c-fos. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 8 |
| Volume Number | 90 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 1993-05-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Asbestos Pharmacology Toxicity Genes, Fos Drug Effects Genes, Jun Pleura Proto-Oncogene Proteins C-fos Biosynthesis Proto-Oncogene Proteins C-jun RNA, Messenger Metabolism Trachea Animals Asbestos, Crocidolite Asbestos, Serpentine Blotting, Northern Cell Division Cell Transformation, Neoplastic Cells, Cultured Cricetinae Dose-Response Relationship, Drug Epithelial Cells Epithelium Physiology Gene Expression Kinetics Models, Biological Cytology Genetics Rats, Inbred F344 Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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