Accumulation of radium in ferruginous protein bodies formed in lung tissue: association of resulting radiation hotspots with malignant mesothelioma and other malignancies

Our plain-English summary of Accumulation of radium in ferruginous protein bodies formed in lung tissue: association of resulting radiation hotspots with malignant mesothelioma and other malignancies, by E. Nakamura, A. Makishima, K. Hagino, et al (Proceedings of the Japan Academy. Series B, Physical and Biological Sciences, 2009).

The study

• Authors: E. Nakamura, A. Makishima, K. Hagino, K. Okabe
• Journal: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
• Published: 2009;85(7):229-39
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

While exposure to fibers and particles has been proposed to be associated with several different lung malignancies including mesothelioma, the mechanism for the carcinogenesis is not fully understood. Along with mineralogical observation, we have analyzed forty-four major and trace elements in extracted asbestos bodies (fibers and proteins attached to them) with coexisting fiber-free ferruginous protein bodies from extirpative lungs of individuals with malignant mesothelioma. These observations together with patients' characteristics suggest that inhaled iron-rich asbestos fibers and dust particles, and excess iron deposited by continuous cigarette smoking would induce ferruginous protein body formation resulting in ferritin aggregates in lung tissue. Chemical analysis of ferruginous protein bodies extracted from lung tissues reveals anomalously high concentrations of radioactive radium, reaching millions of times higher concentration than that of seawater. Continuous and prolonged internal exposure to hotspot ionizing radiation from radium and its daughter nuclides could cause strong and frequent DNA damage in lung tissue, initiate different types of tumour cells, including malignant mesothelioma cells, and may cause cancers.

In plain English

This laboratory study analyzed surgically removed lung tissue from six patients in Japan with malignant pleural mesothelioma, aged 51 to 65. The authors extracted asbestos bodies (fibers coated with iron-rich protein) and fiber-free iron-rich protein bodies. They examined these by electron microscopy and measured 44 elements, including radium-226. The asbestos fibers identified were amosite and crocidolite; glass and silicate fibers also appeared. No chrysotile was found. Three patients were recorded as having asbestos exposure; the other three showed no clear association with it. Assuming the protein was ferritin, the authors estimated radium in the protein bodies at 0.03 to 0.4 nanograms per gram, which they described as millions of times higher than in seawater. Radium was undetectable in reference samples of chrysotile, amosite and crocidolite. The three patients with a smoking history (all had quit) had higher iron levels and more fiber-free protein bodies than the three non-smokers. The authors proposed that radium collecting in these bodies creates radiation "hotspots" that could damage DNA and start tumours, including mesothelioma. They noted that some calculated element concentrations were unrealistically high, mainly because of inadequate sample weights.

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: Laboratory (mineralogical and chemical) analysis of lung tissue from a small series of patients
• Who was studied: Six patients with malignant pleural mesothelioma: four male and two female, aged 51 to 65, living in Yamaguchi, Fukuoka, Aichi and Shiga prefectures, Japan. Their occupations were quarrying industry, insulation industry, asbestos scrapper, railway carriage builder, post office and school teacher. About 5 grams of surgically obtained lung tissue was taken from each patient. The article does not give dates.
• Exposure: The asbestos fibers found in the lungs were the iron-rich amphiboles crocidolite and amosite; glass fibers and unidentifiable silicate fibers were also seen. Asbestos exposure was declared for three patients (E, H, I); the others did not show clear association with asbestos exposure. Three patients had a history of cigarette smoking (35, 40 and about 10 years). All three had quit before surgery: 6 months, 12 months and 30 years before the operation.
• Main results:
  • The only asbestos fibers found were amphiboles (crocidolite and amosite); no chrysotile fibers were found in any of the six patients. Glass fibers and unidentifiable silicate fibers were also observed.
  • The crocidolite-to-amosite ratio varied widely between patients, from 0.05 to 9.0; the authors suggested the patients may have been exposed to fibers from different sources.
  • The authors interpreted the absence of chrysotile as indicating that chrysotile was not involved in the mesothelioma of these six patients.
  • Radium-226 in the ferruginous protein bodies ranged from 0.03 to 0.4 ng per gram, which the authors described as millions of times higher than seawater. These were estimated concentrations: the authors normalized to the iron content of ferritin, assuming all protein separates were ferritin.
  • In the three asbestos reference standards (chrysotile, amosite, crocidolite), radium-226 was below the detection limit.
  • The authors reported that the patients with a history of cigarette smoking (Cases A, H and M, all of whom had quit before surgery) had higher iron concentrations than non-smokers. They also had larger amounts of fiber-free ferruginous protein bodies, with volume judged qualitatively.
  • There was no correlation between asbestos body counts and iron content per dry lung weight.
  • One patient (Case K) showed a gadolinium excess, traced to an MRI contrast agent given about 3 months before surgery. The authors took this as evidence that such elements can be captured and retained.
• The authors' conclusion: The authors proposed that radium accumulating in iron-rich protein bodies in the lung forms radiation hotspots. They suggested these hotspots could repeatedly damage DNA and could initiate tumour cells, including malignant mesothelial cells.
• Limitations the authors state:
  • Major-element concentrations calculated from estimated sample weights were unrealistically high, primarily because the sample weights were inadequate.
  • To normalize trace-element concentrations, the authors assumed that all protein separates were ferritin.

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: Malignant Mesothelioma, Mesothelioma, Carcinogenesis, Asbestos Bodies, Ferritin.

Related studies

• A method for extracting ferruginous bodies from sputum and pulmonary tissue — M.J. Smith, B. Naylor (1972)
• A procedure for the isolation of amosite asbestos and ferruginous bodies from lung tissue and sputum — M.G. Williams, R.F. Dodson, et al. (1982)
• Asbestos and other ferruginous bodies: their formation and clinical significance — A.M. Churg, M.L. Warnock (1981)
• The ultrastructure of asbestos bodies from guinea-pig lungs — J.M. Davis (1964)
• Peroxidase-like activity of ferruginous bodies isolated by exploiting their magnetic property — V. Borelli, E. Trevisan, et al. (2012)
• Relationships between ferruginous bodies and uncoated asbestos fibers in lung tissue — R.F. Dodson, M. O'Sullivan, et al. (1996)

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