Free radical activity associated with the surface of particles: a unifying factor in determining biological activity?

Our plain-English summary of Free radical activity associated with the surface of particles: a unifying factor in determining biological activity?, by K. Donaldson, P.H. Beswick, P.S. Gilmour (Toxicology Letters, 1996).

The study

• Authors: K. Donaldson, P.H. Beswick, P.S. Gilmour
• Journal: Toxicology Letters
• Published: 1996;88(1-3):293-8
• Cited by: 140 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Using a sensitive phi X174 RF plasmid DNA assay, free radical activity was detected at the surface of normal and ultrafine titanium dioxide (TiO2), environmental particles (PM-10), asbestos and a range of man-made fibres. There were differences in the amount of free radical activity that was detected, with ultrafine TiO2 being much more active than normal-sized TiO2; PM-10 also had substantial free radical activity. Amphibole asbestos samples were highly active, whilst man-made fibres were much less active than asbestos. For all of the particles, the DNA damage could be ameliorated by mannitol, showing that hydroxyl radicals were involved. The ability of particles to generate free radicals at or near their surface, and thereby impose oxidant stress in key target cells, could be central to determining their pathogenicity.

In plain English

This was a laboratory test-tube experiment, not a study of people or animals. The authors measured whether different particles produce free radicals (reactive molecules) at their surface. Their test measured breakage of loops of virus DNA. They tested normal-sized and ultrafine titanium dioxide, airborne particles (PM-10) collected in Edinburgh, amosite and crocidolite asbestos, refractory ceramic fibres and glass fibres. All of the particles showed some activity, but the amounts differed. Ultrafine titanium dioxide completely destroyed the intact (supercoiled) form of the DNA even at 50 micrograms per millilitre, the lowest dose in its dose-comparison test. Normal titanium dioxide had modest activity. PM-10 caused marked DNA damage, though the dose could not be measured. Amosite and crocidolite asbestos damaged the DNA, while the man-made fibres caused only small amounts of damage. Mannitol, a substance used to show hydroxyl radicals were involved, reduced the damage. The authors suggested that all particles release free radicals to some degree, and that this could be central to how particles affect lung cells. They noted that the low activity of refractory ceramic fibres argued against a free radical theory of fibre harm.

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 (cell-free) experiment measuring free radical damage to plasmid DNA in a test tube
• Who was studied: Particle samples, not people: normal titanium dioxide (0.5 micrometre), ultrafine titanium dioxide (0.02 micrometre diameter), PM-10 collected at Princes St. Gardens, Edinburgh, UK, long and short amosite asbestos, crocidolite asbestos, refractory ceramic fibres RCFs 1-4 and glass fibres MMVFs 10, 11, 21 and 22
• Exposure: Plasmid DNA (290 ng) was incubated with the particles for 8 hours at 37 degrees C. The fibres were used at equal fibre number. The titanium dioxide dose-comparison test started at 50 micrograms per millilitre, and a separate mannitol test used ultrafine titanium dioxide at 5 micrograms per millilitre. The PM-10 dose was not known.
• Main results:
  • PM-10 caused marked depletion of supercoiled DNA, which was protected by mannitol; the figure legend says hydroxyl radicals accounted for about half of the DNA breakage
  • Normal titanium dioxide had modest ability to break DNA. Ultrafine titanium dioxide caused complete destruction of supercoiled DNA even at 50 micrograms per millilitre, the lowest dose in the dose-comparison test (Fig. 2).
  • At a lower dose of 5 micrograms per millilitre, DNA breakage by ultrafine titanium dioxide was reduced by mannitol
  • Crocidolite and amosite asbestos both depleted supercoiled DNA. This was protected by mannitol and, according to the authors' other study [15], by iron chelation.
  • The man-made fibres (RCFs 1-4 and MMVFs 10, 11, 21 and 22) caused only small amounts of DNA strand breakage. This was not affected by iron chelation but was protected by mannitol (data not shown).
• The authors' conclusion: The authors suggested that all particles can release free radicals at their surface to some degree, with differences between particles. They proposed that this surface activity, and its effect on the cell's redox balance through glutathione depletion, could be central to damage to the lung lining and to gene activation.
• Limitations the authors state:
  • The dose of PM-10 used could not be given because of the inconsistent way the material was harvested from the filter
  • Direct comparison between particle samples is problematic because free radical activity likely depends on surface area, which could differ greatly between samples
  • Refractory ceramic fibres showed low free radical activity although they are considered more pathogenic than MMVFs, which the authors said argues against a free radical theory of fibre pathogenicity

Topics

Medical terms in this study, explained in our Lexicon: Amphibole Asbestos, Hydroxyl Radical.

Related studies

• Detection of surface free radical activity of respirable industrial fibres using supercoiled phi X174 RF1 plasmid DNA — P.S. Gilmour, P.H. Beswick, et al. (1995)
• Supercoiled plasmid DNA as a model target for assessing the generation of free radicals at the surface of fibres — K. Donaldson, P.S. Gilmour, et al. (1995)
• Free radical activity of industrial fibers: role of iron in oxidative stress and activation of transcription factors — P.S. Gilmour, D.M. Brown, et al. (1997)
• Free radical activity of natural and heat treated amphibole asbestos — C. Otero Areán, F. Barceló, et al. (2001)
• Free radical generation in the toxicity of inhaled mineral particles: the role of iron speciation at the surface of asbestos and silica — I. Fenoglio, L. Prandi, et al. (2001)
• Tobacco smoke: involvement of reactive oxygen species and stable free radicals in mechanisms of oxidative damage, carcinogenesis and synergistic effects with other respirable particles — A. Valavanidis, T. Vlachogianni, et al. (2009)

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