Mechanisms of asbestos carcinogenesis and toxicity: the amphibole hypothesis revisited

Our plain-English summary of Mechanisms of asbestos carcinogenesis and toxicity: the amphibole hypothesis revisited, by B.T. Mossman (British Journal of Industrial Medicine, 1993).

The study

• Author: B.T. Mossman
• Journal: British Journal of Industrial Medicine
• Published: 1993;50(8):673-6
• Type of article: Editorial
• Cited by: 31 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Summary of the article

In this editorial the author reviewed experimental evidence on how asbestos causes cancer and cell injury, in light of the "amphibole hypothesis". The editorial noted that mesothelioma incidence varies by fibre type and is highest with crocidolite exposure. It also noted debate over whether mesotheliomas in Quebec chrysotile miners and millers can be attributed to tremolite. Under the hypothesis, fibre durability over latency periods averaging 35 to 40 years is an important but not exclusive factor. The author summarised findings on chromosomal changes in human mesotheliomas, including losses of chromosomes 4, 22 and 9p. Searches for ras and myc mutations were negative, and p53 or retinoblastoma alterations were few; one study found p53 abnormalities in only three of 20 mesothelioma cell lines. Asbestos was not mutagenic in the Ames test, but a human-hamster hybrid cell assay detected large multilocus lesions from chrysotile and crocidolite. Evidence was reviewed that active oxygen species, produced by phagocytic cells in response to long fibres or catalysed by iron on fibre surfaces, mediate asbestos effects. Crocidolite contains about 36% iron by weight, compared with 2%-3% in some chrysotile samples. Work from the author's laboratory showed persistent, dose dependent induction of c-fos and c-jun in mesothelial cells, most pronounced with crocidolite. The author proposed a hypothetical model in which fibre durability, persistence and iron content explain crocidolite's greater pathogenicity. Chrysotile dissolves in the lung and may not persist long enough, whereas minimal biodegradation over rodents' two to three year lifespan may explain similar tumour incidence across fibre types in rodent models.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

This 1993 article is an editorial, not an original study. The author reviewed published laboratory, animal and epidemiological research on how asbestos may cause cancer and cell damage. The author revisited the "amphibole hypothesis": the idea that the amphiboles crocidolite and amosite are more likely than chrysotile to cause mesothelioma because they persist longer in the lung or pleura. Citing other researchers, the editorial said that crocidolite is about 36% iron by weight, compared with 2%-3% in some chrysotile samples. It said iron may help produce active oxygen species that damage cells. It noted that asbestos was not mutagenic in the Ames test, and that one study of 20 mesothelioma cell lines from 17 patients found p53 abnormalities in only three lines. The author's laboratory reported increased expression of the c-fos and c-jun genes in cultured rodent mesothelial cells exposed to asbestos, most pronounced with crocidolite. The author proposed a hypothetical model in which fibre durability and persistence are necessary factors in tumour development, while chrysotile dissolves in the lung.

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: Editorial reviewing published research on the mechanisms of asbestos carcinogenesis and toxicity; no new study population
• Exposure: Asbestos fibre types compared: the amphiboles crocidolite and amosite versus chrysotile; tremolite in Quebec chrysotile mining areas is also mentioned
• Main results:
  • Citing earlier work, the editorial stated that the iron content of crocidolite is about 36% by weight, compared with only 2%-3% in some chrysotile samples
  • The editorial noted that asbestos fibres, unlike chemical carcinogens, are not mutagenic in the Ames test, a bacterial assay
  • Citing another study, the editorial reported that examination of 20 mesothelioma cell lines from 17 patients showed p53 abnormalities in only three lines and no evidence of Ki-ras activation
  • Studies from the author's laboratory found increases in c-fos and c-jun gene expression in cultured rodent mesothelial cells exposed to crocidolite or chrysotile. The changes were most pronounced with crocidolite. This passage is partly cut off in the scanned text
  • The editorial stated that chrysotile undergoes dissolution in the lung and in pleural mesothelial cells, and that this breakdown is probably minimal over the two-to-three-year time frame of rodent tumour development. The author offered this as the reason rodent studies show no striking differences in tumour incidence between asbestos types
• The authors' conclusion: The author presented a hypothetical model emphasising fibre durability and persistence as necessary factors in tumour development. The author offered this model to explain the increased pathogenicity of crocidolite in the development of mesothelioma
• Limitations the authors state:
  • The author described the proposed model of tumour development as a hypothetical construct
  • The author stated that searches for gene mutations in human mesotheliomas are limited by the complexity of genetic changes seen in human tumours

Topics

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

Medical terms in this study, explained in our Lexicon: Carcinogenesis, amphibole hypothesis, Mesothelioma, Crocidolite, Quebec Chrysotile, Tremolite, Latency, Chrysotile.

Related studies

• Asbestos-related cancer and the amphibole hypothesis. The hypothesis is still supported by scientists and scientific data — B.T. Mossman, J.B. Gee (1997)
• Occupational exposure to chrysotile asbestos and cancer risk: a review of the amphibole hypothesis — L.T. Stayner, D.A. Dankovic, et al. (1996)
• The amphibole hypothesis of asbestos-related cancer--gone but not forgotten — M.R. Cullen (1996)
• Asbestos-related cancer and the amphibole hypothesis. The first documentation of the association — J.C. Wagner (1997)
• Asbestos-related cancer and the amphibole hypothesis. The amphibole hypothesis: neither gone nor forgotten — A.M. Langer, R.P. Nolan (1997)
• Effect of size fractionation on the toxicity of amosite and Libby amphibole asbestos — K.E. Duncan, A.J. Ghio, et al. (2010)

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