Mechanisms of asbestos carcinogenesis

Our plain-English summary of Mechanisms of asbestos carcinogenesis, by B.T. Mossman, J.E. Craighead (Environmental Research, 1981).

The study

• Authors: B.T. Mossman, J.E. Craighead
• Journal: Environmental Research
• Published: 1981;25(2):269-80
• Type of article: Review
• Cited by: 61 articles, as counted by NIH iCite
• Read it: PubMed · Publisher
• In J-M's library: Johns-Manville's company medical library held a copy (J-M no. 000759).

In plain English

This 1981 article was a review. It summarized other researchers' animal studies and the authors' own laboratory experiments on how asbestos may contribute to respiratory tract cancer. It did not address mesothelioma. The authors' work used hamster tracheal tissue in organ culture and hamster tracheal lining cells grown in single layers. Chrysotile and crocidolite both injured the lining tissue, and chrysotile did so more severely. The basal cell layer survived and then multiplied, and short fibers built up inside cells. Tissue exposed to crocidolite carrying the chemical 3-methylcholanthrene (3 MC) developed carcinomas after 12 to 52 weeks when implanted into hamsters. Tissue exposed to crocidolite without 3 MC did not. Crocidolite and amosite promoted overgrowth of the lining. In cell cultures, crocidolite alone did not change activity of an enzyme that processes such chemicals (AHH). Crocidolite plus 3 MC roughly doubled it compared with 3 MC alone (mean 170 versus 80 picograms of 3-OH-BP per minute per milligram of protein; P less than 0.005). The authors proposed, as a hypothesis, that asbestos acts as a cocarcinogen.

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: Review summarizing the authors' own laboratory experiments (organ and cell cultures, with implantation into hamsters) and other researchers' animal studies; includes enzyme-activity data in a table
• Who was studied: Explants (organ cultures) of hamster trachea and monolayer cultures of hamster tracheal mucosal (epithelial) cells. Some organ cultures were implanted under the skin of syngeneic hamsters. The review also covers rodent studies by others.
• Exposure: Chrysotile, crocidolite and amosite asbestos applied to tracheal cultures, with and without the polycyclic hydrocarbon 3-methylcholanthrene (3 MC) adsorbed to the fibers. In the enzyme experiment, crocidolite was used at 0.01 and 0.05 mg/ml medium for 24 hours.
• Main results:
  • In tracheal organ cultures, both chrysotile and crocidolite were cytotoxic to the lining tissue. Injury was more severe with chrysotile.
  • At relatively high asbestos concentrations the surface layer sloughed off. The basal cell layer remained intact and then proliferated.
  • Tracheal organ cultures exposed to crocidolite with surface-bound 3 MC, then implanted into hamsters, developed carcinomas after 12 to 52 weeks. Cultures exposed to crocidolite without 3 MC did not develop tumors. Numbers of animals or tumors are not given in this article.
  • The amphiboles crocidolite and amosite promoted hyperplasia (overgrowth) and increased tritiated thymidine uptake in tracheal lining tissue in vitro. Squamous metaplasia also developed.
  • Exposure to asbestos increased activity of the plasma membrane enzyme Na+-K+-dependent ATPase in tracheal lining cells. The enzyme glucose-6-phosphatase was not affected.
  • In hamster tracheal epithelial cell monolayers, AHH enzyme activity was not changed by crocidolite alone.
  • In the same monolayers, mean AHH specific activity was 170 (standard error 4.1) for cells exposed to 3 MC plus crocidolite (0.01 mg/ml). For 3 MC alone it was 80 (standard error 2.4), and for untreated controls 36 (standard error 1.8). Activity was measured as pg 3-OH-BP per minute per mg protein, as means of 6 replicate incubations. The increase over 3 MC alone was reported as significant at P less than 0.005 (Student's t test).
• The authors' conclusion: The authors proposed a hypothetical scheme in which asbestos serves as a cocarcinogen. In this scheme, asbestos carries polycyclic hydrocarbons into basal cells, which the authors call the presumptive progenitors of bronchogenic carcinoma. It also stimulates these cells and causes their dedifferentiation.
• Limitations the authors state:
  • The authors described their finding of asbestos in premalignant tracheal cells as circumstantial, not conclusive, evidence that fiber uptake by cells matters in carcinogenesis.
  • The authors stated that the association of asbestos with newly proliferated basal cells was incompletely understood.
  • The authors stated that the animal studies they reviewed were difficult to evaluate because of differing protocols and incomplete documentation of lesions.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Carcinogenesis.

Related studies

• Carcinoma induction by 3-methylcholanthrene in hamster tracheal tissue implanted in syngeneic animals — J.E. Craighead, B.T. Mossman (1979)
• Mechanism of fiber carcinogenesis: from reactive radical species to silencing of the beta igH3 gene — T.K. Hei, A. Xu, et al. (2006)
• Induction by asbestos fibers of anaphase abnormalities: mechanism for aneuploidy induction and possibly carcinogenesis — T.W. Hesterberg, J.C. Barrett (1985)
• Use of hamster tracheal organ cultures for assessing the cocarcinogenic effects of inorganic particulates on the respiratory epithelium — B.T. Mossman, J.E. Craighead (1979)
• Tests for effect of asbestos on benzo[a]pyrene carcinogenesis in the respiratory tract — L. Miller, W.E. Smith, et al. (1965)
• Implications of multiple mechanisms of carcinogenesis for short-term testing — B.L. Harper, D.L. Morris (1984)

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