Iron associated with asbestos bodies is responsible for the formation of single strand breaks in phi X174 RFI DNA

Our plain-English summary of Iron associated with asbestos bodies is responsible for the formation of single strand breaks in phi X174 RFI DNA, by L.G. Lund, M.G. Williams, R.F. Dodson, et al (Occupational and Environmental Medicine, 1994).

The study

• Authors: L.G. Lund, M.G. Williams, R.F. Dodson, A.E. Aust
• Journal: Occupational and Environmental Medicine
• Published: 1994;51(3):200-4
• Cited by: 51 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The ability of amosite cored asbestos bodies isolated from human lungs to catalyse damage to phi X174 RFI DNA in vitro was measured and compared with that of uncoated amosite fibres with a similar distribution of length. Asbestos bodies (5000 bodies) suspended for 30 minutes in 50 mM NaCl containing 0.5 micrograms phi X174 RFI DNA, pH 7.5, did not catalyse detectable amounts of DNA single strand breaks. Addition of the reducing agent ascorbate (1 mM), however, resulted in single strand breaks in 10% of the DNA. Asbestos bodies in the presence of a low molecular weight chelator (1 mM) and ascorbate catalysed the formation of single strand breaks in 21% of the DNA with citrate or 77% with ethylenediamine tetra-acetic acid (EDTA), suggesting that mobilisation of iron may increase damage to DNA. Preincubation for 24 hours with desferrioxamine B, which binds iron (Fe (III)) and renders it redox inactive, completely inhibited the reactivity of asbestos bodies with DNA, strongly suggesting that iron was responsible. Amosite fibres (5000 fibres/reaction), with a similar length distribution to that of the asbestos bodies, did not catalyse detectable amounts of single strand breaks in DNA under identical reaction conditions. The results of the present study strongly suggest that iron deposits on the amosite core asbestos bodies were responsible for the formation of DNA single strand breaks in vitro. Mobilisation of iron by chelators seemed to enhance the reactivity of asbestos bodies with DNA. It has been postulated that the in vivo deposition of the coat material on to fibres may be an attempt by the lung defenses to isolate the fibre from the lung surface and thus offer a protective mechanism from physical irritation. These results suggest, however, that the iron that is deposited on asbestos fibres in vivo may be reactive, potentially increasing the damage to biomolecules, such as DNA, above that of the uncoated fibres.

In plain English

This was a laboratory (test-tube) experiment. Asbestos bodies are asbestos fibres that have become coated in the lung with material that includes iron. The authors took amosite-cored asbestos bodies from the lung tissue of a dead 68 year old insulator who had adenocarcinoma and a documented occupational exposure to amosite only. They compared these bodies with uncoated amosite fibres of similar length, 5000 per reaction, for their ability to cause single strand breaks in a purified laboratory DNA called phiX174 RFI DNA. With the reducing agent ascorbate, the asbestos bodies caused breaks in 10% of the DNA. Adding the chelators citrate or EDTA raised this to 21% and 77%. The uncoated amosite fibres caused no detectable breaks under the same conditions, and neither the bodies nor the fibres produced detectable breaks without ascorbate. Desferrioxamine B, which binds iron, completely blocked the damage. The authors concluded that iron deposited on asbestos fibres in the body may be reactive and may cause more damage to cellular molecules than the uncoated fibres, rather than less. They noted that the bodies' larger surface area could not be corrected for, and that the isolation process might have removed parts of the coating.

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) experiment comparing coated asbestos bodies with uncoated fibres
• Who was studied: Amosite asbestos bodies isolated from the lung tissue of one dead 68 year old insulator with adenocarcinoma who had a documented occupational exposure to amosite only. These were compared with sized uncoated amosite fibres from a sample provided by the National Institute of Environmental Health Sciences.
• Exposure: Amosite-cored asbestos bodies or similarly sized uncoated amosite fibres (5000 per reaction), incubated for 30 minutes with 0.5 micrograms phiX174 RFI DNA, with 1 mM ascorbate and/or 1 mM chelator (citrate or EDTA). In some tests the bodies were preincubated for 24 hours with desferrioxamine B (10 mM).
• Main results:
  • Asbestos bodies with ascorbate caused single strand breaks in 10% (SD 4) of the DNA. The authors described this as very low but statistically significant (p less than 0.025, one sided Student's t test).
  • Adding citrate raised breaks caused by asbestos bodies to 21% (SD 5) of the DNA, and adding EDTA raised them to 77% (SD 7). This was an increase of up to 7.7-fold.
  • Uncoated amosite fibres (5000 fibres per reaction) caused no detectable single strand breaks, with or without a chelator.
  • Without ascorbate, no single strand breaks were detected with either asbestos bodies or amosite fibres. The authors did not show these data.
  • The iron-binding agent desferrioxamine B completely blocked the DNA breaks caused by asbestos bodies, with or without citrate or EDTA.
  • The ethanol and bleach treatment used to isolate the bodies did not change amosite's reactivity. At 1 mg/ml, untreated amosite caused breaks in 21% of the DNA and treated amosite in 19%. With EDTA, the figures were 52% and 50%.
  • The asbestos bodies ranged from 17 to 244 micrometres in length, and the sized amosite fibres from 10 to 147 micrometres.
• The authors' conclusion: The authors concluded that iron deposited on asbestos fibres in the body may be reactive. They concluded that the greater surface area and iron availability of asbestos bodies may lead to more damage to cellular macromolecules, rather than less, as had previously been proposed.
• Limitations the authors state:
  • The authors could not correct for the much greater diameter of the asbestos bodies caused by their coating. They stated that the larger surface area very likely contributed to the greater DNA damage.
  • The isolation procedure may have removed the mucopolysaccharides or proteins of the coat. How these coat components affect iron reactivity in the body is not known.
  • EDTA, one of the chelators used, is not present in the body.

Topics

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

Medical terms in this study, explained in our Lexicon: Asbestos Bodies, Amosite, Desferrioxamine B, Deposition.

Related studies

• Iron mobilization from crocidolite asbestos greatly enhances crocidolite-dependent formation of DNA single-strand breaks in phi X174 RFI DNA — L.G. Lund, A.E. Aust (1992)
• The effect of iron binding on the ability of crocidolite asbestos to catalyze DNA single-strand breaks — J.A. Hardy, A.E. Aust (1995)
• Asbestos causes DNA strand breaks in cultured pulmonary epithelial cells: role of iron-catalyzed free radicals — D.W. Kamp, V.A. Israbian, et al. (1995)
• Modulation of DNA single-strand breaks by intracellular glutathione in human lung cells exposed to asbestos fibers — A. Puhakka, T. Ollikainen, et al. (2002)
• Formation of asbestos bodies under the influence of parenteral iron overload — S. Narang, J.L. Kaw, et al. (1978)
• Using in vitro iron deposition on asbestos to model asbestos bodies formed in human lung — Z. Shen, D. Bosbach, et al. (2000)

Browse more research in Occupational and Environmental Medicine, or return to medical research.