Persistent induction of c-fos and c-jun expression by asbestos

Our plain-English summary of Persistent induction of c-fos and c-jun expression by asbestos, by N.H. Heintz, Y.M. Janssen, B.T. Mossman (Proceedings of the National Academy of Sciences of the United States of America, 1993).

The study

• Authors: N.H. Heintz, Y.M. Janssen, B.T. Mossman
• Journal: Proceedings of the National Academy of Sciences of the United States of America
• Published: 1993;90(8):3299-303
• Cited by: 175 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This was a laboratory study of cells, not people. The authors exposed rat pleural mesothelial cells and a hamster tracheal epithelial cell line to crocidolite or chrysotile asbestos. They studied untreated cells and cells given TPA, a comparison chemical. They measured mRNA levels from two growth-related genes, c-fos and c-jun. In the rat cells, c-fos and c-jun mRNA rose steadily from 2 hours of crocidolite exposure through at least 24 hours. At 24 hours, levels were 2- to 5-fold higher than in untreated or TPA-treated cultures; TPA gave only a brief peak at 1 hour. Both fiber types gave dose-dependent increases. By weight the two looked similar, but by fiber number crocidolite was more potent. Polystyrene beads and nonfibrous riebeckite caused no increases. In the hamster cells, asbestos raised c-jun mRNA but not c-fos mRNA. In both cell types, asbestos increased AP-1 DNA-binding activity, meaning more protein bound to specific gene-control sites on DNA. The authors proposed that asbestos, by persistently activating the early response gene pathway, may cause chronic cell proliferation contributing to cancer in lung and pleura.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) cell culture experiment
• Who was studied: Rat pleural mesothelial (RPM) cells isolated from the parietal pleura of Fischer 344 rats, and a hamster tracheal epithelial (HTE) cell line from the tracheal epithelium of a neonatal hamster
• Exposure: Reference samples of NIEHS processed crocidolite and NIEHS chrysotile (Jeffrey Mines, Quebec) asbestos, added to cultures at 1.25 to 5.0 micrograms per square centimetre of dish. TPA at 100 ng/ml served as a comparison agent. Riebeckite (a nonfibrous particle chemically similar to crocidolite) and polystyrene beads were used to test the role of fiber shape.
• Main results:
  • In rat pleural mesothelial cells, c-fos and c-jun mRNA levels increased steadily after 2 hours of crocidolite exposure, for at least 24 hours
  • In rat pleural mesothelial cells, c-fos and c-jun mRNA levels after 24 hours of crocidolite exposure were 2- to 5-fold higher than in control cultures or TPA-treated cultures
  • In rat pleural mesothelial cells, TPA caused c-fos mRNA to peak after 1 hour and then fall quickly back to control levels
  • In rat pleural mesothelial cells, crocidolite and chrysotile appeared similar in inducing c-fos and c-jun when dose was measured by fiber mass. Measured by number of fibers per unit area, crocidolite was the more potent inducer, because chrysotile has more fibers per unit mass.
  • Polystyrene beads and riebeckite did not increase c-fos or c-jun mRNA in rat pleural mesothelial cells
  • In hamster tracheal epithelial cells, c-fos mRNA was not elevated at any time after the first 30 minutes following TPA, chrysotile or crocidolite
  • In hamster tracheal epithelial cells, crocidolite raised c-jun mRNA from 4 hours, with levels increasing steadily for at least 24 hours
  • In rat pleural mesothelial cells, AP-1 DNA-binding activity induced by asbestos after 24 hours was about twice that seen with TPA
  • In hamster tracheal epithelial cells, asbestos exposure was accompanied by increases in proteins that bind the AP-1 DNA sequence, even though c-fos was not induced
• The authors' conclusion: The authors proposed a model in which asbestos, by persistently activating the early response gene pathway, may induce chronic cell proliferation that contributes to carcinogenesis in lung and pleura

Mines named here

Asbestos mines this study is about. Each mine's page says who ran it, when it worked, and what it produced.

• Jeffrey mine, Asbestos, Quebec

All asbestos mines

Topics

The National Library of Medicine indexes this study under subjects our site covers: Chrysotile, Crocidolite.

Medical terms in this study, explained in our Lexicon: Carcinogenesis, Mesothelial Cells, Crocidolite, Chrysotile, Causation, Pleural Mesothelioma.

Related studies

• Induction of c-fos and c-jun proto-oncogenes in target cells of the lung and pleura by carcinogenic fibers — Y.M. Janssen, N.H. Heintz, et al. (1994)
• Patterns of c-fos and c-jun proto-oncogene expression, apoptosis, and proliferation in rat pleural mesothelial cells exposed to erionite or asbestos fibers — C.R. Timblin, G.D. Guthrie, et al. (1998)
• Growth factor responses and protooncogene expression of murine mesothelial cell lines derived from asbestos-induced mesotheliomas — L.A. Goodglick, C.A. Vaslet, et al. (1997)
• Asbestos induces nuclear factor kappa B (NF-kappa B) DNA-binding activity and NF-kappa B-dependent gene expression in tracheal epithelial cells — Y.M. Janssen, A. Barchowsky, et al. (1995)
• Asbestos-induced phosphorylation of epidermal growth factor receptor is linked to c-fos and apoptosis — C.L. Zanella, C.R. Timblin, et al. (1999)
• Hydrolysis of inositol phospholipids precedes cellular proliferation in asbestos-stimulated tracheobronchial epithelial cells — A. Sesko, M. Cabot, et al. (1990)

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