Persistent induction of c-fos and c-jun expression by asbestos
- Univ. of Vermont College of Medicine, Burlington (United States)
- Univ. of Vermont College of Medicine, Burlington (United States) Univ. of Limburg, Maastricht (Netherlands)
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. 30 refs., 5 figs.
- OSTI ID:
- 6466396
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 90:8; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ANIMAL CELLS
CARCINOGENESIS
ASBESTOS
BIOLOGICAL EFFECTS
CARCINOGENS
BIOLOGICAL PATHWAYS
CELL PROLIFERATION
DOSE-RESPONSE RELATIONSHIPS
HAMSTERS
RATS
RODENTS
TRANSCRIPTION FACTORS
ANIMALS
MAMMALS
PATHOGENESIS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology