Mechanisms of asbestos-induced squamous metaplasia in tracheobronchial epithelial cells

Our plain-English summary of Mechanisms of asbestos-induced squamous metaplasia in tracheobronchial epithelial cells, by G. Cameron, C.D. Woodworth, S. Edmondson, et al (Environmental Health Perspectives, 1989).

The study

• Authors: G. Cameron, C.D. Woodworth, S. Edmondson, B.T. Mossman
• Journal: Environmental Health Perspectives
• Published: 1989;80:101-8
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Within 1 to 4 weeks after exposure to asbestos, differentiated rodent and human tracheobronchial epithelial cells in organ culture undergo squamous metaplasia, a putative preneoplastic lesion characterized by conversion of mucociliary cell types to keratinizing cells. The exogenous addition of retinal acetate (RA) to culture medium of hamster tracheal organ cultures reverses preestablished, asbestos-induced squamous metaplasia, although data suggest that the effectiveness of RA decreases as the length of time between exposure to asbestos and initial application of RA increases. alpha-Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), inhibits squamous metaplasia caused by asbestos or vitamin A deficiency, whereas addition of methylglyoxal bis(guanylhydrazone) (MGBG), a structural analog of spermidine and inhibitor of S-adenosylmethionine decarboxylase, causes an enhancement of metaplasia under both circumstances. Basal cell hyperplasia and increased incorporation of 3H-thymidine by tracheal epithelial cells also are seen after addition of the polyamines, putrescine or spermidine, to tracheal organ cultures, an observation supporting the importance of polyamines in the development of this lesion. The use of retinoids and inhibitors of ODC could be promising as preventive and/or therapeutic approaches for individuals at high risk for development of asbestos-associated diseases.

In plain English

This was a laboratory study of pieces of windpipe (trachea) taken from female golden Syrian hamsters and kept alive in culture dishes. It looked at squamous metaplasia, a change in the lining cells that the authors call a possible step toward cancer. Some tissue pieces were exposed for 1 hour to crocidolite asbestos and others to the chemical benzo(a)pyrene (BaP). Crocidolite significantly increased metaplasia compared with untreated tissue; BaP did not. A vitamin A derivative, retinal acetate, added after the changes had formed, reduced metaplasia in a dose-dependent way in all groups. The data suggested it worked less well on asbestos-exposed tissue when started at 5 weeks rather than 3 weeks (p less than 0.09). DFMO, a drug that blocks production of growth molecules called polyamines, prevented the rise in metaplasia after crocidolite. It did not appear to affect metaplasia caused by a vitamin A-deficient medium. Two polyamines, putrescine and spermidine, raised the share of lining cells taking up 3H-thymidine, a measure of DNA synthesis. The authors concluded that DFMO or retinoids appear to prevent or reverse asbestos-associated metaplasia in vitro.

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 experiment on hamster tracheal organ cultures (tissue kept alive in culture dishes, not living animals or people)
• Who was studied: Tracheal explants (tissue pieces) from female golden Syrian hamsters aged 6-8 weeks, cultured in groups of 9-15 explants (14-19 per group in the DNA-synthesis experiments)
• Exposure: UICC reference sample crocidolite asbestos applied once for 1 hour at the start of culture (dose printed as both 4 µg/mL and 4 mg/mL). Other explants received benzo(a)pyrene three times weekly for 3 weeks. Some explants were also treated with retinal acetate (10 to the minus 7 or 10 to the minus 8 M), DFMO, MGBG, or the polyamines putrescine, spermidine or spermine.
• Main results:
  • Explants exposed to asbestos had significantly more squamous metaplasia than controls (p less than 0.001).
  • Explants exposed to BaP did not show an increase in metaplasia compared with controls.
  • Retinal acetate reversed squamous metaplasia in a dose-dependent manner (p less than 0.001) in pooled control, BaP and asbestos groups. The amount of metaplasia remained more striking in asbestos-exposed explants.
  • The data suggested retinal acetate was less effective at reversing asbestos-induced metaplasia when given at 5 weeks than at 3 weeks (p less than 0.09).
  • Crocidolite alone or MGBG alone increased squamous metaplasia compared with controls (p less than 0.05). No increase was seen when crocidolite was combined with DFMO, and the authors stated that DFMO appears to inhibit both asbestos- and MGBG-induced metaplasia.
  • In vitamin A-deficient cultures (no asbestos), DFMO had no effect on metaplasia. MGBG alone or MGBG with DFMO significantly increased metaplasia (p less than 0.05).
  • Putrescine (1 and 10 mM) and spermidine (1 mM) significantly increased the percentage of epithelial cells incorporating 3H-thymidine, a measure of DNA synthesis (p less than 0.05). Mean labeled cells were 6.96% for putrescine 1 mM (n=19), 7.28% for putrescine 10 mM (n=14) and 6.95% for spermidine 1 mM (n=15), versus 2.42% in controls (n=19). Spermine 1 mM (2.36%, n=16) did not raise labeling.
  • Spermine and spermidine were toxic to tracheal epithelium at 10 mM (data not shown).
• The authors' conclusion: The authors concluded that depleting polyamines with DFMO, or treatment with retinoids, appears to be an effective means of preventing and/or reversing asbestos-associated squamous metaplasia in vitro. They suggested these agents may be rewarding as preventive or therapeutic approaches to lung disease in humans.

Topics

Medical terms in this study, explained in our Lexicon: Mucociliary Clearance.

Related studies

• Ozone enhances the uptake of mineral particles by tracheobronchial epithelial cells in organ culture — A. Churg, M. Brauer, et al. (1996)
• Hydrolysis of inositol phospholipids precedes cellular proliferation in asbestos-stimulated tracheobronchial epithelial cells — A. Sesko, M. Cabot, et al. (1990)
• Asbestos and benzo[a]pyrene act synergistically to induce squamous metaplasia and incorporation of [3H]thymidine in hamster tracheal epithelium — B.T. Mossman, A. Eastman, et al. (1984)
• Fiber deposition in the tracheobronchial region: experimental measurements — Y. Zhou, W.C. Su, et al. (2007)
• Ascorbic acid inhibits the squamous metaplasia that results from treatment of tracheal explants with asbestos or benzo[a]pyrene-coated asbestos — G. Holtz, E. Bresnick (1988)
• Analysis of asbestos-induced gene expression changes in bronchiolar epithelial cells using laser capture microdissection and quantitative reverse transcriptase-polymerase chain reaction — C.B. Manning, B.T. Mossman, et al. (2006)

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