Induction of c-fos and c-jun proto-oncogenes in target cells of the lung and pleura by carcinogenic fibers

Our plain-English summary of Induction of c-fos and c-jun proto-oncogenes in target cells of the lung and pleura by carcinogenic fibers, by Y.M. Janssen, N.H. Heintz, J.P. Marsh, et al (American Journal of Respiratory Cell and Molecular Biology, 1994).

The study

• Authors: Y.M. Janssen, N.H. Heintz, J.P. Marsh, P.J. Borm, B.T. Mossman
• Journal: American Journal of Respiratory Cell and Molecular Biology
• Published: 1994;11(5):522-30
• Cited by: 82 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

To study mechanisms of cell proliferation by asbestos and nonasbestos fibers, we examined the effects of these agents on the mRNA levels of c-fos and c-jun and ornithine decarboxylase (ODC) in hamster tracheal epithelial (HTE) cells and rat pleural mesothelial (RPM) cells, the progenitor cells of bronchogenic carcinoma and mesothelioma, respectively. In comparison with crocidolite asbestos, increases in c-jun mRNA were less striking in HTE cells after exposure to man-made vitreous fiber-10 (MMVF-10) or refractory ceramic fiber-1 (RCF-1). No c-fos mRNA was detected in HTE cells after exposure to particulates, but exposure of HTE cells to H2O2 caused striking increases in c-fos and c-jun, which preceded increases in ODC mRNA. Increases in ODC mRNA were also observed in HTE cells after exposure to nonasbestos fibers, whereas only crocidolite asbestos caused elevations in ODC mRNA in RPM cells. In RPM cells, crocidolite and chrysotile asbestos caused increases in mRNA levels of both c-fos and c-jun. No increases in proto-oncogene induction were observed using MMVF-10 or RCF-1 at nontoxic concentrations (< or = 5 micrograms/cm2 dish). Moreover, erionite, a fiber extremely potent in the causation of mesothelioma in humans, caused more dramatic elevations in c-fos and c-jun. Nonfibrous particles (riebeckite, polystyrene beads) did not alter proto-oncogene expression in these cell types, suggesting that the fibrous geometry of particulates is critical in the induction of c-fos and c-jun.

In plain English

This was a laboratory study of cells grown in dishes, not a study of people. The authors exposed hamster tracheal epithelial (HTE) cells and rat pleural mesothelial (RPM) cells to several materials. They describe these cells as the ones that give rise to bronchogenic carcinoma and mesothelioma. The materials were crocidolite and chrysotile asbestos, two man-made fibers (MMVF-10 and refractory ceramic fiber RCF-1), erionite, nonfibrous riebeckite, polystyrene beads and hydrogen peroxide. The authors measured messenger RNA for the c-fos and c-jun genes and for ornithine decarboxylase (ODC), which are linked to cell growth. In HTE cells, crocidolite raised c-jun 2- to 3-fold after 24 hours, but no c-fos was detected. MMVF-10 and RCF-1 caused only modest c-jun changes, and riebeckite caused none. Hydrogen peroxide at 100 micromolar raised both genes most at 2 hours. In RPM cells, crocidolite raised ODC (p less than 0.05) and c-fos and c-jun. There, the man-made fibers raised c-fos and c-jun only at clearly toxic concentrations. Erionite raised c-fos and c-jun more than crocidolite did. The authors concluded that fibrous shape appears critical to inducing c-fos and c-jun.

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) experiment on cultured animal cells, measuring gene activity (mRNA) by Northern blot
• Who was studied: Cultured hamster tracheal epithelial (HTE) cells from a neonatal hamster and rat pleural mesothelial (RPM) cells from the parietal pleura of Fischer 344 rats; no human subjects
• Exposure: Crocidolite and chrysotile asbestos (reference samples), man-made vitreous fiber-10 (MMVF-10), refractory ceramic fiber-1 (RCF-1), erionite from Rome, Oregon, nonfibrous riebeckite and polystyrene beads, and hydrogen peroxide
• Main results:
  • In HTE cells, crocidolite asbestos at 5 or 25 micrograms per square centimeter for 24 hours caused 2- to 3-fold increases in c-jun mRNA
  • In HTE cells, MMVF-10 and RCF-1 produced only modest changes in c-jun mRNA compared with asbestos
  • In HTE cells, riebeckite (nonfibrous, chemically identical to crocidolite) did not alter c-jun mRNA
  • No c-fos mRNA was detected in HTE cells exposed to asbestos
  • In HTE cells exposed to 100 micromolar hydrogen peroxide, c-fos and c-jun mRNA were highest at 2 hours and fell toward control levels by 24 hours
  • In HTE cells, ODC mRNA rose 2-fold at 8 hours and 2.8-fold at 24 hours with crocidolite, compared with 4- and 2.2-fold with 100 micromolar hydrogen peroxide
  • In HTE cells, ODC elevations were less dramatic with MMVF-10, RCF-1 or riebeckite than with crocidolite
  • In RPM cells after 24 hours, ODC mRNA was increased by crocidolite at both concentrations (P less than 0.05) but not by chrysotile or polystyrene beads
  • In RPM cells, crocidolite at 2.5 micrograms per square centimeter for 8 hours increased c-fos and c-jun mRNA
  • In RPM cells, MMVF-10, RCF-1 and riebeckite at lower concentrations did not alter c-fos or c-jun mRNA
  • In RPM cells, MMVF-10 and RCF-1 increased c-fos and c-jun mRNA at 25 micrograms per square centimeter, which the authors describe as obviously cytotoxic concentrations
  • In RPM cells, erionite caused larger increases in c-fos and c-jun mRNA than crocidolite asbestos
  • HTE cells appeared more resistant to the toxic effects of all fibers tested than RPM cells
• The authors' conclusion: The authors concluded that, because nonfibrous particles did not alter proto-oncogene expression, the fibrous shape of particles appears critical in inducing c-fos and c-jun

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: Pleura, Carcinogenic, Bronchogenic Carcinoma, Mesothelioma, Crocidolite, Vitreous, Chrysotile, erionite.

Related studies

• Persistent induction of c-fos and c-jun expression by asbestos — N.H. Heintz, Y.M. Janssen, et al. (1993)
• 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)
• Novel cell imaging techniques show induction of apoptosis and proliferation in mesothelial cells by asbestos — J.L. Goldberg, C.L. Zanella, et al. (1997)
• Effects of Aramid, a high strength synthetic fiber, on respiratory cells in vitro — J.P. Marsh, B.T. Mossman, et al. (1994)

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