An investigation of the internal morphology of asbestos ferruginous bodies: constraining their role in the onset of malignant mesothelioma

Our plain-English summary of An investigation of the internal morphology of asbestos ferruginous bodies: constraining their role in the onset of malignant mesothelioma, by M.L. Avramescu, C. Potiszil, T. Kunihiro, et al (Particle and Fibre Toxicology, 2023).

The study

• Authors: M.L. Avramescu, C. Potiszil, T. Kunihiro, K. Okabe, E. Nakamura
• Journal: Particle and Fibre Toxicology
• Published: 2023;20(1):19
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Asbestos is a fibrous mineral that was widely used in the past. However, asbestos inhalation is associated with an aggressive type of cancer known as malignant mesothelioma (MM). After inhalation, an iron-rich coat forms around the asbestos fibres, together the coat and fibre are termed an "asbestos ferruginous body" (AFB). AFBs are the main features associated with asbestos-induced MM. Whilst several studies have investigated the external morphology of AFBs, none have characterised the internal morphology. Here, cross-sections of multiple AFBs from two smokers and two non-smokers are compared to investigate the effects of smoking on the onset and growth of AFBs. Morphological and chemical observations of AFBs were undertaken by transmission electron microscopy, energy dispersive x-ray spectroscopy and selected area diffraction.

Results: The AFBs of all patients were composed of concentric layers of 2-line or 6-line ferrihydrite, with small spherical features being observed on the outside of the AFBs and within the cross-sections. The spherical components are of a similar size to Fe-rich inclusions found within macrophages from mice injected with asbestos fibres in a previous study. As such, the spherical components composing the AFBs may result from the deposition of Fe-rich inclusions during frustrated phagocytosis. The AFBs were also variable in terms of their Fe, P and Ca abundances, with some layers recording higher Fe concentrations (dense layers), whilst others lower Fe concentrations (porous layers). Furthermore, smokers were found to have smaller and overall denser AFBs than non-smokers.

Conclusions: The AFBs of smokers and non-smokers show differences in their morphology, indicating they grew in lung environments that experienced disparate conditions. Both the asbestos fibres of smokers and non-smokers were likely subjected to frustrated phagocytosis and accreted mucopolysaccharides, resulting in Fe accumulation and AFB formation. However, smokers' AFBs experienced a more uniform Fe-supply within the lung environment compared to non-smokers, likely due to Fe complexation from cigarette smoke, yielding denser, smaller and more Fe-rich AFBs. Moreover, the lack of any non-ferrihydrite Fe phases in the AFBs may indicate that the ferritin shell was intact, and that ROS may not be the main driver for the onset of MM.

© 2023. The Author(s).

In plain English

This laboratory study examined asbestos bodies: asbestos fibres coated with iron-rich material. They came from stored lung samples of four people with malignant mesothelioma, from Yamaguchi Ube Medical Centre, Japan. Two patients were smokers and two were non-smokers. Identified fibres were amosite or crocidolite; one fibre could not be evaluated and one body had none. The authors sliced bodies with a focused ion beam and examined their interiors by electron microscopy, chemical analysis and diffraction. In every patient the coats had concentric layers, some dense, some porous. Their iron was in the form of ferrihydrite; no other iron minerals were detected. The smokers' bodies were generally smaller and richer in iron: non-smokers' bodies had a mean iron content 6.5% less than smokers' bodies. The authors noted that the number of samples was limited. They suggested that iron complexation by cigarette smoke made lung iron more available, giving smokers' bodies a more continuous iron supply. They also suggested that reactive oxygen species may not be the main driver of mesothelioma onset, proposing radiation from adsorbed radium as another possible 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: Laboratory electron-microscopy study of asbestos ferruginous bodies (asbestos bodies) taken from previously collected human lung samples. Bodies were sliced with a focused ion beam and examined by transmission electron microscopy, energy dispersive X-ray spectroscopy and selected area diffraction.
• Who was studied: Four malignant mesothelioma patients selected from six in an earlier study (Nakamura et al., 2009): two non-smokers (N1, N2) and two smokers (S1, S2). Lung samples came from Yamaguchi Ube Medical Centre, Japan. Four asbestos bodies from each of N1, N2 and S1 and three from S2 were analysed.
• Exposure: Asbestos fibres found inside the asbestos bodies: amosite in all identified fibres from N1 and S1 and in one from N2; crocidolite in three from N2 and in all identified fibres from S2. The fibre of body 2 from S1 could not be evaluated, and body 2 from S2 had no fibre. Smoking status was compared.
• Main results:
  • In all four patients, the asbestos bodies were made of concentric layers. Some layers were porous (with small holes) and others were dense.
  • In the smokers, the asbestos bodies tended to have a thick, porous layer close to or immediately around the fibre.
  • The cross-section diameters of the asbestos bodies were generally larger in the non-smoking patients than in the smoking patients.
  • The non-smoking patients had larger and more porous layers in their asbestos bodies than the smoking patients.
  • The mean iron abundance in asbestos bodies from the non-smoking patients was 6.5% less than in those from the smoking patients. Table 2 means, by weight percent: N1 59.14, N2 59.20, S1 63.13, S2 63.43.
  • Within each asbestos body, iron, phosphorus and calcium were lower in the fibre than in the rest of the body.
  • In all studied asbestos bodies the iron was in the form of ferrihydrite (2-line or 6-line), and no other iron minerals were detected. There was no obvious difference in ferrihydrite type between smokers and non-smokers.
  • Small spherical components, 50 to 170 nm across, were seen on and within the asbestos bodies. The authors considered them too small to be intact parts of macrophages.
• The authors' conclusion: The authors concluded that asbestos bodies of smokers and non-smokers differ in internal structure. They suggested this was likely because complexation of iron by cigarette smoke increased iron mobilisation, giving smokers' bodies a more continuous iron supply. They also proposed that the absence of non-ferrihydrite iron phases may mean the ferritin shell was intact, so that mechanisms other than reactive oxygen species, such as DNA damage from radiation from adsorbed radium, may be more likely in the onset of malignant mesothelioma.
• Limitations the authors state:
  • The authors stated that the number of samples was limited.
  • Some diffraction patterns read as 6-line ferrihydrite may instead be a transition phase between 6-line and 2-line ferrihydrite.
  • The authors stated that what the differences between smokers' and non-smokers' asbestos bodies mean for the start of cancer and mesothelioma is not yet understood.

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: Ferruginous body, Mesothelioma, Transmission Electron Microscopy (TEM), energy dispersive X-ray spectroscopy (EDS), Ferrihydrite, Macrophage, Deposition, Frustrated Phagocytosis.

Related studies

• Peroxidase-like activity of ferruginous bodies isolated by exploiting their magnetic property — V. Borelli, E. Trevisan, et al. (2012)
• Accumulation of radium in ferruginous protein bodies formed in lung tissue: association of resulting radiation hotspots with malignant mesothelioma and other malignancies — E. Nakamura, A. Makishima, et al. (2009)
• Ferruginous bodies and pulmonary fibrosis in dead low to moderately exposed asbestos cement workers: histological examination — L.G. Johansson, M.P. Albin, et al. (1987)
• Closing the knowledge gap on the composition of the asbestos bodies — F. Bardelli, C. Giacobbe, et al. (2023)
• The clinical significance of ferruginous bodies in sputa — J.W. McLarty, S.D. Greenberg, et al. (1980)
• Relationships between ferruginous bodies and uncoated asbestos fibers in lung tissue — R.F. Dodson, M. O'Sullivan, et al. (1996)

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