A Nontarget Mechanism to Explain Carcinogenesis Following α-Irradiation

Our plain-English summary of A Nontarget Mechanism to Explain Carcinogenesis Following α-Irradiation, by N.D. Priest (Dose-response, 2019).

The study

• Author: N.D. Priest
• Journal: Dose-response
• Published: 2019;17(4):1559325819893195
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

This commentary highlights the published data on the metabolic processes that lead to the development of cancer following intakes of asbestos and chemical agents. Following exposure to both, the key initiating event is cell injury leading to cell death that may further lead to inflammation, fibrosis, and cancer. Since α-particle transits also kill cells, it is suggested that cell death and inflammation will also trigger carcinogenesis within tissues irradiated by these particles. Such an explanation would be consistent with the inflammation and fibrosis seen in tumor-bearing tissues irradiated by radon-222, radium-226, thorium-232, plutonium-239, and other α-emitting radionuclides. It would also provide an explanation for dose-related changes in latency and in the similar dose-responses for the same tissue in differently sized species.

© The Author(s) 2019.

In plain English

This was a commentary, not a new study, and it reported no new data. The author argued that cancer following alpha-particle radiation from radionuclides may arise mainly through tissue damage, cell death and chronic inflammation, rather than through direct damage to DNA in individual cells. As a model, the author described a mechanism proposed in a 2010 publication for what the commentary calls asbestos-induced lung cancer. In that mechanism, asbestos kills mesothelial cells, which release HMGB1, a protein that starts and promotes inflammation. Inflammatory signals then let some DNA-damaged mesothelial cells survive, and cytokines may further promote their division. The author suggested that alpha particles, which also kill cells, could act through similar pathways. The author also drew on a published pathway for chemical-induced liver fibrosis and on earlier work describing fibrosis alongside cancer in tissues exposed to alpha-emitters. The author concluded that this offered a plausible mechanism. The author speculated that, if chronic inflammation is a required step in alpha-induced cancer, very low doses might cause too little tissue damage to sustain it, and no cancer would be produced.

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 (an opinion piece drawing on previously published data); no new study was carried out
• Who was studied: No study population; the commentary discusses previously published human and animal research
• Exposure: Alpha-particle radiation from radionuclides (such as radon-222, radium-226, thorium-232 and plutonium-239), compared with asbestos fibers (fiber type not specified) and chemical agents
• Main results:
  • The author described a mechanism proposed in a 2010 publication for asbestos, beginning with death of mesothelial cells and release of HMGB1, and argued that alpha particles and asbestos share common pathways involving chronic inflammation
  • In the described asbestos mechanism, a survival pathway lets some DNA-damaged mesothelial cells survive, and cytokines may further promote the division of mutation-bearing cells
  • Citing earlier studies of lung cancer after plutonium exposure in rats, beagle dogs and Mayak workers, the author argued that average tissue dose and the tissue damage it causes, rather than damage within individual cells, matters for cancer induction
  • The author drew on a published pathway for chemical-induced liver fibrosis, in which cell injury and death lead to fibrosis
  • Citing earlier reports of fibrosis occurring together with cancer in lung, liver and skeleton after exposure to alpha-emitters, the author stated that these observations fit a common inflammation-induced trigger for both
  • The author speculated that, if chronic inflammation is an obligate step in alpha-induced cancer, very low levels of tissue irradiation might cause too little tissue damage to sustain chronic inflammation, and no cancer would be produced
• The authors' conclusion: The author concluded that the commentary provides a plausible mechanism for cancer arising from chronic inflammation and tissue damage after alpha-particle irradiation

Topics

Medical terms in this study, explained in our Lexicon: Carcinogenesis, Inflammation, Fibrosis, Latency, Dose-response relationship.

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