Asbestos related malignancy and the Cairns hypothesis

Our plain-English summary of Asbestos related malignancy and the Cairns hypothesis, by K. Browne (British Journal of Industrial Medicine, 1991).

The study

• Author: K. Browne
• Journal: British Journal of Industrial Medicine
• Published: 1991;48(2):73-6
• Type of article: Editorial
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text
• In J-M's library: Johns-Manville's company medical library held a copy (J-M no. 003932).

Summary of the article

This editorial, by Kevin Browne of the Department of Occupational Medicine, National Heart and Lung Institute, London, examined whether asbestos-related cancer could be explained by Cairns' hypothesis. That hypothesis holds that cells have evolved a natural mechanism protecting against harmful mutations arising during cell division, and that chronic cell proliferation can disrupt it. Drawing on published animal, pathological and epidemiological evidence, the author noted that asbestos is not a mutagen, that attempts to show direct malignant transformation had failed or required unrealistic in vitro conditions, and that fibres shorter than 5 µm appeared to be neither fibrogenic nor carcinogenic. He described asbestosis as resulting from mediators released by macrophages after incomplete ingestion of long fibres, with a generally accepted threshold of 25 fibre/ml years. He argued that the same excess of growth factors drives the epithelial proliferation leading to lung cancer. In support he cited increased lung cancer in fibrosis from other causes, and two studies finding increased lung cancer risk only in the presence of asbestosis. He interpreted the more than additive effect of smoking as asbestos acting as a promoter. For mesothelioma he cited inflammatory change preceding tumours, a suggested threshold of about five fibres/ml-years for amphiboles, a longer latent period at lower doses reported by four research groups, and tumours produced by non-asbestos fibres. The author concluded that asbestos-related malignancy does not result from direct genotoxic action, is subject to threshold and dose-response effects, and is consistent with disruption of the protective mechanism suggested by Cairns.

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 article is an editorial, not a report of new research. The author reviewed published evidence to argue that asbestos causes cancer indirectly, through a protective mechanism against harmful mutations described by Cairns that chronic cell growth can disrupt. The author argued that asbestos is not a mutagen and that it is carcinogenic only when its fibres exceed a certain length. Citing animal studies and some human data, the editorial stated that fibres shorter than 5 micrometres are neither fibrogenic nor carcinogenic. In the author's account, long fibres that lung macrophages (scavenger cells) cannot fully engulf cause a chronic release of chemical signals, leading to fibrosis and uncontrolled cell growth. The author cited two studies finding that lung cancer risk was increased only when asbestosis was present. The editorial also cited a suggested threshold of about five fibres/ml-years for mesothelioma from amphibole asbestos, and reports from four research groups that lower injected fibre doses gave fewer mesotheliomas after longer latent periods. The author concluded that asbestosis, lung cancer and mesothelioma result from this single effect of long fibres, not from direct genetic damage.

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 (a narrative review and argument based on other published studies; no new data)
• Who was studied: No study population of its own. The editorial discussed published experimental animal studies and human epidemiological and pathological studies by other researchers.
• Exposure: Asbestos in general, with emphasis on fibre length. The editorial also discussed amosite, chrysotile, amphibole asbestos, tremolite, and non-asbestos durable fibres of comparable dimensions.
• Main results:
  • The author stated that asbestos is not a mutagen. According to the author, attempts to show that it directly transforms bronchial epithelium or mesothelium had failed or had required unrealistic in vitro conditions.
  • Citing experimental animal evidence with some support from human epidemiology, the author stated that the evidence is compelling that fibres shorter than 5 micrometres are neither fibrogenic nor carcinogenic.
  • The author stated that lung inflammation produced by macrophages interacting with short fibres has been shown to be transient. In contrast, fibres too long to be completely ingested may produce lifelong effects.
  • The author stated that, in humans, a threshold for cumulative exposure of 25 fibre/ml years, below which clinical asbestosis will not appear, has been generally accepted.
  • The author cited two studies designed to test the link between fibrosis and cancer. Both found that lung cancer risk was increased only when there was radiological or pathological evidence of asbestosis.
  • The author cited evidence that patients with cryptogenic fibrosing alveolitis, or with diffuse interstitial pulmonary fibrosis secondary to other systemic diseases, show a greatly increased incidence of lung cancer. The author offered this as evidence that no carcinogenic action specific to asbestos is needed.
  • The author cited a review of animal and human evidence suggesting a threshold of about five fibres/ml-years for mesothelioma from exposure to amphibole asbestos.
  • The author reported, from a personal communication (JMG Davis), that amosite injected into the peritoneum in several doses produced more mesotheliomas than the same total dose given as a single injection.
  • The author cited four research groups reporting that a lower injected fibre dose reduced the number of mesotheliomas and also lengthened the average latent period. The author argued this is incompatible with asbestos acting as an initiator.
  • The author suggested that chrysotile is rarely associated with mesothelioma in humans because it tends to fragment, which allows macrophages to ingest it completely.
• The authors' conclusion: The author concluded that asbestosis, lung cancer and mesothelioma result from a single effect of long fibres: release of macrophage mediators after incomplete ingestion. In the author's view, the malignant changes do not result from direct genotoxic action, and their probability is subject to threshold and dose response effects. The author judged the evidence consistent with the Cairns hypothesis.

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Transformation, Fibrogenic, Carcinogenic, Macrophage, Lung Cancer, Fibrosis, Mesothelioma, Amphibole Group.

Related studies

• An overload hypothesis for pulmonary clearance of UICC amosite fibres inhaled by rats — R.E. Bolton, J.H. Vincent, et al. (1983)
• 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 hypothesis is still supported by scientists and scientific data — B.T. Mossman, J.B. Gee (1997)
• Asbestos-related cancer and the amphibole hypothesis. The amphibole hypothesis: neither gone nor forgotten — A.M. Langer, R.P. Nolan (1997)
• Role of nitrative and oxidative DNA damage in inflammation-related carcinogenesis — M. Murata, R. Thanan, et al. (2012)

Browse more research in British Journal of Industrial Medicine, or return to medical research.