Commentary on "Mechanisms of asbestos-induced carcinogenesis" published in 2009

Our plain-English summary of Commentary on "Mechanisms of asbestos-induced carcinogenesis" published in 2009, by S. Toyokuni (Nagoya Journal of Medical Science, 2023).

The study

• Author: S. Toyokuni
• Journal: Nagoya Journal of Medical Science
• Published: 2023;85(1):13-15
• Type of article: Comment
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Summary of the article

In this commentary, written for the journal's 100th anniversary series on highly cited articles, the author looked back on his 2009 review of the mechanisms of asbestos-induced carcinogenesis. He noted that asbestos was used in Japan until 2006 and is still used in many developing countries, although the International Agency for Research on Cancer declared all asbestos a definite human carcinogen in 1987. He restated that the review summarized the mechanism as three processes: persistent free radical generation by macrophages that scavenge fibers (frustrated phagocytosis), intense phagocytic activity of mesothelial cells, and adsorption of proteins such as hemoglobin and histone onto asbestos. The review also proposed why chrysotile, which contains no iron, can cause similar oxidative DNA damage. He then summarized later work from his group. Chrysotile-induced mesothelioma in rats showed excess iron pathology with homozygous deletion of the p16Ink4a gene. Multiwalled carbon nanotubes of about 50 nm diameter showed pathologic processes similar to asbestos. Iron removal by chelating agents or phlebotomy could work as prevention in preclinical animal models. Macrophages dying by ferroptosis released iron-loaded ferritin in exosomes, which induced oxidative DNA damage in mesothelial cells. He described this as a novel indirect mechanism of asbestos-induced mesothelial carcinogenesis.

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 was a short commentary, not a new study, and it reported no new data. The author looked back on the author's own highly cited 2009 review, "Mechanisms of asbestos-induced carcinogenesis." The author restated that the review summarized three proposed processes by which asbestos may cause mesothelioma. First, macrophages (scavenger cells) take up asbestos fibers and keep producing free radicals. Second, mesothelial cells show unexpectedly intense engulfing activity. Third, specific proteins, such as hemoglobin and histone, stick to asbestos surfaces. The review had also suggested why chrysotile, which contains no iron itself, can cause similar oxidative DNA damage, pointing to its high hemolytic (red-blood-cell-destroying) activity. The author then described later laboratory work published elsewhere. Chrysotile-induced mesothelioma in rats showed excess iron and loss of both copies of the p16Ink4a gene. Removing iron could work as prevention in preclinical animal models. Macrophages that could not cope with asbestos died by ferroptosis and released iron-loaded ferritin in exosomes, and mesothelial cells receiving these exosomes showed induced oxidative DNA damage. The author called this a novel indirect mechanism.

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: commentary by the author on the author's own 2009 review article (no new data)
• Who was studied: No people or animals were studied in this commentary; it discusses the 2009 review and later laboratory work published elsewhere, including work in rats
• Exposure: Asbestos fibers in general, with discussion of iron-containing asbestos and of chrysotile (white asbestos, which contains no iron itself); multiwalled carbon nanotubes are discussed for comparison
• Main results:
  • The author restated that the 2009 review summarized three proposed processes: macrophages scavenging asbestos fibers, which leads to persistent free radical generation; unexpected intense phagocytic activity of mesothelial cells; and adsorption of specific proteins (for example hemoglobin and histone) on the asbestos surface
  • The author stated that a combination of the second and third processes could explain asbestos's mutagenic activity in mesothelial cells, through iron-loaded asbestos being attracted to chromosomal histones
  • The 2009 review suggested that chrysotile's high hemolytic activity was the key to how it causes oxidative DNA damage despite containing no iron itself
  • Later work from the author's group, cited in the commentary, found that chrysotile-induced malignant mesothelioma in rats showed excess iron pathology with homozygous deletion of the p16Ink4a tumor suppressor gene
  • Cited work found that multiwalled carbon nanotubes of about 50 nm diameter show pathologic processes similar to those of asbestos
  • The author stated that iron removal, by iron chelating agents or phlebotomy, could work as prevention of asbestos-induced mesothelial carcinogenesis, at least in preclinical animal models
  • Cited work found that macrophages exposed to asbestos they cannot cope with die by ferroptosis and release iron-loaded ferritin in exosomes, which are taken up by mesothelial cells where oxidative DNA damage is induced
• The authors' conclusion: The author described the ferroptosis and exosome pathway as a novel indirect mechanism of asbestos-induced mesothelial carcinogenesis. The author stated that the 2009 review acted as a detonator for further study of these mechanisms.

Topics

Medical terms in this study, explained in our Lexicon: Carcinogenesis, Macrophage, Frustrated Phagocytosis, Mesothelial Cells, Chrysotile, Mesothelioma, Pathology, Homozygous Deletion.

Related studies

• Mechanisms of asbestos-induced carcinogenesis — S. Toyokuni (2009)
• Ferroptosis-dependent extracellular vesicles from macrophage contribute to asbestos-induced mesothelial carcinogenesis through loading ferritin — F. Ito, K. Kato, et al. (2021)
• Iron addiction with ferroptosis-resistance in asbestos-induced mesothelial carcinogenesis: Toward the era of mesothelioma prevention — S. Toyokuni (2019)
• Dual preventive benefits of iron elimination by desferal in asbestos-induced mesothelial carcinogenesis — L. Jiang, S.H. Chew, et al. (2016)
• Global overexpression of divalent metal transporter 1 delays crocidolite-induced mesothelial carcinogenesis in male mice — S. Funahashi, Y. Okazaki, et al. (2018)
• Decoding the molecular enigma behind asbestos and fibrous nanomaterial-induced carcinogenesis — S. Toyokuni, Y. Kong (2025)

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