Mechanisms of asbestos-induced carcinogenesis

Our plain-English summary of Mechanisms of asbestos-induced carcinogenesis, by S. Toyokuni (Nagoya Journal of Medical Science, 2009).

The study

• Author: S. Toyokuni
• Journal: Nagoya Journal of Medical Science
• Published: 2009;71(1-2):1-10
• Type of article: Review
• Cited by: 103 articles, as counted by NIH iCite
• Read it: PubMed · Free full text

Abstract

Respiratory exposure to asbestos fibers has been associated with diffuse malignant mesothelioma (DMM) in humans. Despite advancements in the molecular analyses of human DMM and the development of animal models, the carcinogenic mechanisms of the disease remain unclear. There are basically three hypotheses regarding the pathogenesis of asbestos-induced DMM, which may be summarized as follows: (1) the "oxidative stress theory" is based on the fact that phagocytic cells that engulf asbestos fibers produce large amounts of free radicals due to their inability to digest the fibers, and epidemiological studies indicating that iron-containing asbestos fibers appear more carcinogenic; (2) the "chromosome tangling theory" postulates that asbestos fibers damage chromosomes when cells divide; and (3) the "theory of adsorption of many specific proteins as well as carcinogenic molecules" states that asbestos fibers in vivo concentrate proteins or chemicals including the components of cigarette smoke. Elucidation of the major mechanisms underlying DMM would be helpful for the development of novel strategies to prevent DMM induction in people who have already been exposed to asbestos.

In plain English

This article was an invited review by a single author at Nagoya University, Japan. It was not a new study. It summarized the types of asbestos: the amphiboles crocidolite, amosite, tremolite, anthophyllite and actinolite, and the serpentine chrysotile. It also covered the history and epidemiology of diffuse malignant mesothelioma, genetic changes found in human mesothelioma, and animal models. The review described a general consensus that the risk of mesothelioma and lung cancer is greatest with crocidolite, less with amosite, and apparently less with chrysotile. It then set out three hypotheses for how asbestos causes mesothelioma. The first, an "oxidative stress theory," involves iron and immune cells that engulf fibers. The second, a "chromosome tangling theory," holds that fibers damage chromosomes when cells divide. The third, an "adsorption theory," holds that fibers concentrate proteins or chemicals, including cigarette smoke components. The author cited earlier work from the author's own laboratory. That work reported that amosite and crocidolite are good catalysts for producing free radicals, and that chrysotile concentrates iron in surrounding tissue. The author stated a belief that catalytic iron plays an important role. The author suggested that changing iron status is one possible prevention measure for people already exposed.

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: Invited narrative review (no new data collected for this article)
• Who was studied: No study population; the review covered published literature on asbestos fibers and on the history, epidemiology, genomics, animal models and mechanisms of diffuse malignant mesothelioma (DMM)
• Exposure: Respiratory exposure to asbestos fibers in general, including the amphiboles (crocidolite, amosite, tremolite, anthophyllite, actinolite) and the serpentine chrysotile
• Main results:
  • The review described three current hypotheses for how asbestos causes DMM: the oxidative stress theory, the chromosome tangling theory, and the adsorption theory
  • The review reported a general consensus, drawn from the epidemiological literature, that risk of mesothelioma and lung cancer is greatest with crocidolite, less with amosite, and apparently less with chrysotile
  • The author cited earlier work from the author's laboratory (reference 51) reporting that amosite and crocidolite are good catalysts for free-radical generation
  • The same earlier laboratory work reported that asbestos fibers, including crocidolite, were taken up by cultured cells and entered both the cytoplasm and the nucleus. The author offered this as relevant to the chromosome tangling hypothesis
  • The same earlier laboratory work reported that chrysotile, which does not contain iron as a constituent, concentrates iron in surrounding tissue, probably via hemolysis
• The authors' conclusion: The author concluded that the mechanism is complex. The author stated a belief that catalytic iron plays an important role, and suggested that modulating iron status is one measure for preventing DMM in people already exposed. The shape, size and adsorbing nature of fibers also appear critically important.

Topics

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

Medical terms in this study, explained in our Lexicon: Carcinogenesis, Malignant Mesothelioma, Carcinogenic, Oxidative Stress.

Related studies

• Commentary on "Mechanisms of asbestos-induced carcinogenesis" published in 2009 — S. Toyokuni (2023)
• Implications of multiple mechanisms of carcinogenesis for short-term testing — B.L. Harper, D.L. Morris (1984)
• mRNA expression patterns in different stages of asbestos-induced carcinogenesis in rats — H. Sandhu, W. Dehnen, et al. (2000)
• Asbestos exposure affects poly(ADP-ribose) polymerase-1 activity: role in asbestos-induced carcinogenesis — M. Tomasetti, M. Amati, et al. (2011)
• Cellular and molecular mechanisms of asbestos-induced fibrosis — R. Robledo, B. Mossman (1999)
• Cellular mechanisms of reactive oxygen metabolite generation from human polymorphonuclear leukocytes induced by crocidolite asbestos — T. Ishizaki, E. Yano, et al. (1997)

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