Asbestos induced oxidative injury to DNA

Our plain-English summary of Asbestos induced oxidative injury to DNA, by N. Mahmood, S.G. Khan, S. Ali, et al (The Annals of Occupational Hygiene, 1993).

The study

• Authors: N. Mahmood, S.G. Khan, S. Ali, M. Athar, Q. Rahman
• Journal: The Annals of Occupational Hygiene
• Published: 1993;37(3):315-9
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

DNA-damaging effects of asbestos in the presence of organic peroxides and hydroperoxides were investigated. The destabilization of the secondary structure of DNA, damage to deoxyribose sugar and DNA fidelity were measured, respectively, by S-1 nuclease hydrolysis, the formation of thiobarbituric acid (TBA)-reacting species and a melting temperature (Tm) profile using calf thymus DNA. S-1 nuclease hydrolysis and Tm determinations have shown that the presence of benzoylperoxide (BOOB), cumene hydroperoxide (COOH) or tertiary-butyl hydroperoxide (t-BOOH) increased asbestos-mediated DNA damage by a large factor compared either to asbestos alone or to peroxide or hydroperoxide alone. However, no formation of TBA-reacting species could be observed in this system. The quenchers of reactive oxygen species (ROS) afforded protection against DNA damage. These results suggest that asbestos in the presence of organic peroxides and hydroperoxides damage the DNA which is mediated by the generation of oxygen free radicals. The significance of these results in relation to the development of cancer of the respiratory tract among the asbestos exposed population is discussed.

In plain English

This short communication reported a laboratory experiment on DNA in test tubes, not a study of people or animals. The authors incubated calf thymus DNA for 20 hours with UICC chrysotile, UICC crocidolite or Indian chrysotile asbestos. Each mixture also contained one of three organic peroxides or hydroperoxides, which the authors used as models of lipid peroxides. They measured DNA damage mainly by how easily an enzyme (S-1 nuclease) broke the DNA down and by changes in its melting temperature. Asbestos alone or peroxide alone had little effect. With cumene hydroperoxide alone, 5.3% of DNA was broken down. At the highest asbestos dose with cumene hydroperoxide, the figures were 17.9% for Indian chrysotile, 27.6% for UICC chrysotile and 37.5% for UICC crocidolite. Damage rose with asbestos dose, and crocidolite had the greatest effect. Asbestos plus the peroxides markedly lowered the DNA's melting temperature. Oxygen free-radical quenchers and the iron chelator desferal gave varying protection. The authors concluded that asbestos generates oxygen radicals from these peroxides that may damage DNA, and that these changes may be related to lung cancer in exposed individuals.

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: In vitro (test-tube) laboratory experiment, published as a short communication
• Who was studied: No people or animals; the material studied was calf thymus DNA (commercial, from Sigma Chemical Company), with results from four individual experiments per value
• Exposure: UICC standard reference chrysotile and crocidolite, and Indian chrysotile from a local asbestos factory (particle size below 30 micrometres), at 5 mg in 2 ml in the main experiments (1.25 to 5.00 mg in dose tests). Each was combined with benzoylperoxide, cumene hydroperoxide or tertiary-butyl hydroperoxide at 40 mM, at 37°C for 20 hours. Titanium dioxide was used as a comparison dust.
• Main results:
  • Asbestos alone or peroxide/hydroperoxide alone had little effect on DNA breakdown compared with untreated control DNA
  • With cumene hydroperoxide (40 mM), the percentage of DNA hydrolysed was 2.0 (plus or minus 0.08) for control DNA and 5.3 (plus or minus 0.11) for DNA plus cumene hydroperoxide. At 1.25, 2.50 and 5.00 mg the figures were: titanium dioxide 3.9, 4.5 and 6.1; Indian chrysotile 14.0, 15.6 and 17.9; UICC chrysotile 16.0, 20.5 and 27.6; UICC crocidolite 19.0, 23.4 and 37.5. All asbestos values were p less than 0.001 compared with control DNA plus cumene hydroperoxide.
  • Under these conditions crocidolite had a greater effect than the other varieties of asbestos, and the effect depended on asbestos dose
  • Control DNA had a mid-range melting temperature of 85°C. Cumene hydroperoxide, benzoylperoxide and tertiary-butyl hydroperoxide alone only slightly altered it, to 84, 82 and 86°C respectively. With asbestos present, all the peroxides and hydroperoxides markedly lowered the melting temperature (shown in a figure; no numbers given).
  • Various oxygen radical quenchers (including DMSO, histidine, sodium azide, cytochrome c, mannitol and sodium benzoate) gave different degrees of protection against DNA damage, and desferal, an iron chelator, also protected
  • No meaningful formation of TBA-reacting species was found, which the authors took to mean the deoxyribose sugar of DNA was not damaged
• The authors' conclusion: The authors concluded that asbestos mediates the generation of oxygen radicals from peroxides and hydroperoxides, that these radicals may damage DNA, and that these changes may be related to induction of lung cancer in exposed individuals

Topics

Medical terms in this study, explained in our Lexicon: Reactive Oxygen Species (ROS).

Related studies

• 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)
• Mechanism of asbestos-mediated DNA damage: role of heme and heme proteins — Q. Rahman, N. Mahmood, et al. (1997)
• Mitochondria-derived reactive intermediate species mediate asbestos-induced genotoxicity and oxidative stress-responsive signaling pathways — S.X. Huang, M.A. Partridge, et al. (2012)
• Mechanisms of the genotoxicity of crocidolite asbestos in mammalian cells: implication from mutation patterns induced by reactive oxygen species — A. Xu, H. Zhou, et al. (2002)
• Characteristics and modifying factors of asbestos-induced oxidative DNA damage — L. Jiang, H. Nagai, et al. (2008)
• Beta-carotene metabolites enhance inflammation-induced oxidative DNA damage in lung epithelial cells — Y.G. van Helden, J. Keijer, et al. (2009)

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