Asbestos surface provides a niche for oxidative modification

Our plain-English summary of Asbestos surface provides a niche for oxidative modification, by H. Nagai, T. Ishihara, W.H. Lee, et al (Cancer Science, 2011).

The study

• Authors: H. Nagai, T. Ishihara, W.H. Lee, H. Ohara, Y. Okazaki, K. Okawa, S. Toyokuni
• Journal: Cancer Science
• Published: 2011;102(12):2118-25
• Cited by: 66 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Asbestos is a potent carcinogen associated with increased risks of malignant mesothelioma and lung cancer in humans. Although the mechanism of carcinogenesis remains elusive, the physicochemical characteristics of asbestos play a role in the progression of asbestos-induced diseases. Among these characteristics, a high capacity to adsorb and accommodate biomolecules on its abundant surface area has been linked to cellular and genetic toxicity. Several previous studies identified asbestos-interacting proteins. Here, with the use of matrix-assisted laser desorption ionization-time of flight mass spectrometry, we systematically identified proteins from various lysates that adsorbed to the surface of commercially used asbestos and classified them into the following groups: chromatin/nucleotide/RNA-binding proteins, ribosomal proteins, cytoprotective proteins, cytoskeleton-associated proteins, histones and hemoglobin. The surfaces of crocidolite and amosite, two iron-rich types of asbestos, caused more protein scissions and oxidative modifications than that of chrysotile by in situ-generated 4-hydroxy-2-nonenal. In contrast, we confirmed the intense hemolytic activity of chrysotile and found that hemoglobin attached to chrysotile, but not silica, can work as a catalyst to induce oxidative DNA damage. This process generates 8-hydroxy-2'-deoxyguanosine and thus corroborates the involvement of iron in the carcinogenicity of chrysotile. This evidence demonstrates that all three types of asbestos adsorb DNA and specific proteins, providing a niche for oxidative modification via catalytic iron. Therefore, considering the affinity of asbestos for histones/DNA and the internalization of asbestos into mesothelial cells, our results suggest a novel hypothetical mechanism causing genetic alterations during asbestos-induced carcinogenesis.

© 2011 Japanese Cancer Association.

In plain English

This laboratory study examined the surfaces of three standard (UICC) asbestos types: chrysotile, crocidolite and amosite. Silica powder was used for comparison. The authors mixed the fibers with extracts of rat tissues and of human mesothelial cells (MeT5A) and identified the proteins that stuck to them. They sorted 99 of 128 such proteins into eight categories, including histones, ribosomal proteins and hemoglobin. Chrysotile bound the most protein and the most DNA. All three asbestos types caused oxidative changes (by 4-hydroxy-2-nonenal) in bound proteins, more so the iron-rich crocidolite and amosite. Silica and chrysotile broke open red blood cells far more than crocidolite and amosite did. Hemoglobin bound to asbestos but not to silica, and it raised the iron-driven catalytic activity of chrysotile and crocidolite. DNA showed the oxidative damage marker 8-OHdG on crocidolite, and on hemoglobin-treated chrysotile in the presence of hydrogen peroxide. Three hours after chrysotile or crocidolite was instilled into the airways of mice or rats, chrysotile touched red blood cells and hemoglobin lay alongside crocidolite. The authors proposed, as a hypothesis, that the asbestos surface provides a niche for oxidative modification during carcinogenesis.

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 (in vitro) experiments identifying proteins and DNA that bind to asbestos and measuring their oxidative modification, plus a short-term animal experiment in which asbestos suspension was instilled into the airways
• Who was studied: No human subjects. The materials studied were protein extracts (lysates) from rat lung, liver, kidney, brain and tunica vaginalis, and from MeT5A human mesothelial cells, plus DNA and red blood cells. In the in vivo part, mice or rats had chrysotile or crocidolite suspension instilled into their airways, and their lungs were examined 3 hours later.
• Exposure: UICC chrysotile, crocidolite and amosite asbestos suspended in saline, compared with silica powder
• Main results:
  • Chrysotile bound the largest total amount of protein, followed by crocidolite, amosite and silica.
  • Of 128 asbestos-interacting proteins identified, 99 were classified into eight categories: chromatin-binding (9), nucleotide-binding (10), RNA-binding (14), ribosomal (24), cytoprotective (9), cytoskeleton-associated (26), histones (4) and hemoglobin subunits (3).
  • All three asbestos types induced 4-hydroxy-2-nonenal (HNE) modification of adsorbed proteins. Crocidolite and amosite, described as containing approximately 30% iron, induced more of this modification than chrysotile.
  • Silica showed the strongest hemolytic (red-blood-cell-destroying) activity, followed by chrysotile. Crocidolite and amosite were hemolytic at a much lower level (approximately 200-fold less).
  • Hemoglobin bound to asbestos but not to silica. After hemoglobin adsorption, chrysotile and crocidolite showed increased catalytic iron activity (P less than 0.01 relative to the negative control), while silica did not.
  • Chrysotile adsorbed the most DNA, followed by silica, crocidolite and amosite.
  • DNA adsorbed by crocidolite was oxidized to 8-OHdG after 3 hours at 37 degrees C. Adding hemoglobin to chrysotile enhanced DNA oxidation in the presence of hydrogen peroxide.
  • Three hours after chrysotile or crocidolite suspension was instilled into the airways of mice or rats, chrysotile fibers were directly interacting with red blood cells, and hemoglobin was colocalized with crocidolite.
• The authors' conclusion: The authors proposed that asbestos not only adsorbs proteins and DNA but also provides a niche for oxidative reactions, which they presented as a hypothetical mechanism for genetic changes in asbestos-induced carcinogenesis. They stated that further studies are necessary to re-evaluate the risk posed by chrysotile exposure for lung cancer and mesothelioma.
• Limitations the authors state:
  • The authors stated that it remains unclear to what extent the direct interaction between red blood cells or hemoglobin and asbestos contributes to oxidative damage in surrounding tissue.
  • The authors noted that the specificity of protein binding to asbestos is much weaker than that of protein-protein interactions.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Amosite, Chrysotile, Crocidolite.

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Lung Cancer, Mechanism of Carcinogenesis, Crocidolite, Amosite, Chrysotile, Mesothelial Cells, Carcinogenesis.

Related studies

• Detection of 8-oxo-2'-deoxyguanosine, a marker of oxidative DNA damage, in culture medium from human mesothelial cells exposed to crocidolite asbestos — Q. Chen, J. Marsh, et al. (1996)
• Forsterite exposure causes less oxidative DNA damage and lung injury than chrysotile exposure in rats — A. Takata, H. Yamauchi, et al. (2009)
• Characteristics and modifying factors of asbestos-induced oxidative DNA damage — L. Jiang, H. Nagai, et al. (2008)
• 8-hydroxy-2' -deoxyguanosine (8-OHdG): A critical biomarker of oxidative stress and carcinogenesis — A. Valavanidis, T. Vlachogianni, et al. (2009)
• Patterns of 8-hydroxydeoxyguanosine formation in DNA and indications of oxidative stress in rat and human pleural mesothelial cells after exposure to crocidolite asbestos — H. Fung, Y.W. Kow, et al. (1997)
• Soil fungi reduce the iron content and the DNA damaging effects of asbestos fibers — S. Daghino, F. Turci, et al. (2006)

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