Role of oxidants in DNA damage. Hydroxyl radical mediates the synergistic DNA damaging effects of asbestos and cigarette smoke

Our plain-English summary of Role of oxidants in DNA damage. Hydroxyl radical mediates the synergistic DNA damaging effects of asbestos and cigarette smoke, by J.H. Jackson, I.U. Schraufstatter, P.A. Hyslop, et al (The Journal of Clinical Investigation, 1987).

The study

• Authors: J.H. Jackson, I.U. Schraufstatter, P.A. Hyslop, K. Vosbeck, R. Sauerheber, S.A. Weitzman, C.G. Cochrane
• Journal: The Journal of Clinical Investigation
• Published: 1987;80(4):1090-5
• Cited by: 115 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The mechanism by which cigarette smoking and asbestos exposure synergistically increase the incidence of lung cancer is unknown. We hypothesized that cigarette smoke and asbestos might synergistically increase DNA damage. To test this hypothesis we exposed isolated bacteriophage PM2 DNA to cigarette smoke and/or asbestos, and assessed DNA strand breaks as an index of DNA damage. Our results supported our hypothesis. 78 +/- 12% of the DNA exposed to both cigarette smoke and asbestos developed strand breaks, while only 9.8 +/- 7.0 or 4.3 +/- 3.3% of the DNA exposed to cigarette smoke or asbestos, respectively, developed strand breaks under the conditions of the experiment. Our experimental evidence suggested that cigarette smoke and asbestos synergistically increased DNA damage by stimulating .OH formation. First, significant amounts of .OH were detected by electron paramagnetic resonance (EPR) in DNA mixtures containing both cigarette smoke and asbestos, but no .OH was detected in mixtures containing cigarette smoke alone or asbestos alone. Second, the .OH scavengers, dimethylsulfoxide (DMSO), mannitol, or Na benzoate decreased both .OH detection by EPR and strand breaks in DNA mixtures exposed to cigarette smoke and asbestos. Third, the H2O2 scavenger, catalase, and the iron chelators, 1,10-phenanthroline and desferrithiocin, decreased both .OH detection and strand breaks in DNA mixtures exposed to cigarette smoke and asbestos. These latter findings suggest that iron contained in asbestos may catalyze the formation of .OH from H2O2 generated by cigarette smoke. In summary, our study indicates that cigarette smoke and asbestos synergistically increase DNA damage and suggests that this synergism may involve .OH production.

In plain English

This was a laboratory experiment on isolated DNA, not a study of people. The authors exposed DNA from a bacteriophage (a virus called PM2) to crocidolite asbestos, to a cigarette smoke solution, or to both, and then measured breaks in the DNA strands. Under the experiment's conditions, 78 plus or minus 12% of DNA exposed to both developed strand breaks. The figure was 9.8 plus or minus 7.0% with smoke alone and 4.3 plus or minus 3.3% with asbestos alone. The combined figure was significantly greater than the sum of the two. A highly reactive form of oxygen, the hydroxyl radical, was detected in smoke-plus-asbestos mixtures but not with either alone. Chemicals that remove hydroxyl radicals or hydrogen peroxide, or that bind iron, reduced both the hydroxyl radical signal and the DNA breaks. The authors concluded that iron in the asbestos may help form hydroxyl radicals from oxidants made by cigarette smoke. They suggested this could help explain the higher lung cancer rates in smokers exposed to asbestos. They noted that other metals could not be excluded.

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 laboratory experiment on isolated DNA (cell-free), measuring DNA strand breaks and hydroxyl radical production by electron paramagnetic resonance
• Who was studied: Isolated closed circular DNA from bacteriophage PM2 (0.8 micrograms per reaction mixture); each value came from four separate experiments performed in triplicate; no human or animal subjects
• Exposure: 0.05 mg crocidolite asbestos (UICC reference standard sample), 10 microliters of smoke solution made by bubbling smoke from one commercial filter cigarette through 6 ml of buffered saline for 5 minutes, 65 micromolar hydrogen peroxide, and/or 30 micromolar iron sulfate (FeSO4), alone or in combination, for 60 minutes at room temperature
• Main results:
  • DNA with strand breaks: 9.8 plus or minus 7.0% with cigarette smoke alone, 4.3 plus or minus 3.3% with asbestos alone, 5.3 plus or minus 5.5% with FeSO4 alone (means plus or minus standard deviation)
  • 78 plus or minus 12% of DNA exposed to both cigarette smoke and asbestos developed strand breaks, and 86 plus or minus 12% with cigarette smoke and FeSO4
  • 6.5 plus or minus 5.3% of DNA exposed to hydrogen peroxide alone developed strand breaks, compared with 24 plus or minus 6.3% with hydrogen peroxide and asbestos and 25 plus or minus 8.1% with hydrogen peroxide and FeSO4
  • Each combination (smoke plus asbestos, smoke plus FeSO4, hydrogen peroxide plus asbestos, hydrogen peroxide plus FeSO4) gave values significantly greater (P less than 0.05) than the sums of the values for their separate components
  • With smoke plus asbestos, adding DMSO, mannitol, sodium benzoate, catalase, 1,10-phenanthroline or desferrithiocin cut strand breaks to 0, 5.5 plus or minus 6.4, 1.5 plus or minus 3, 4.8 plus or minus 7.1, 4.0 plus or minus 5.7 and 0% respectively; superoxide dismutase did not decrease strand breaks
  • The hydroxyl radical signal was detected in DNA mixtures with cigarette smoke and asbestos together, but not with cigarette smoke alone or asbestos alone
  • In smoke-plus-asbestos mixtures, catalase and the two iron chelators completely abolished the hydroxyl radical signal; mannitol only slightly decreased it
• The authors' conclusion: The authors concluded that asbestos particles synergistically increased strand breaks in isolated DNA exposed to cigarette smoke, likely by stimulating hydroxyl radical production with iron contained in the asbestos. They suggested this could help explain the increased lung cancer incidence in cigarette smokers exposed to significant amounts of asbestos.
• Limitations the authors state:
  • The iron chelators used are not totally specific for iron, and the authors could not exclude a role for other metal contaminants
  • Small amounts of hydroxyl radical may have been produced with cigarette smoke alone but been below the detection limit
  • Further studies are needed to establish the exact role of DNA damage in carcinogenesis

Topics

Medical terms in this study, explained in our Lexicon: Hydroxyl Radical, Asbestos Exposure, Lung Cancer.

Related studies

• A study of the synergistic interaction of asbestos fibers with cigarette tar extracts for the generation of hydroxyl radicals in aqueous buffer solution — A. Valavanidis, H. Balomenou, et al. (1996)
• Asbestos catalyzes hydroxyl and superoxide radical generation from hydrogen peroxide — S.A. Weitzman, P. Graceffa (1984)
• Generation of hydroxyl radical by crocidolite asbestos is proportional to surface [Fe3+] — A.J. Ghio, J. Zhang, et al. (1992)
• Fiber-induced hydroxyl radical formation: correlation with mesothelioma induction in rats and humans — K.R. Maples, N.F. Johnson (1992)
• 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)
• Rat pleural mesothelial cells show damage after exposure to external but not internal cigarette smoke — H.S. Sekhon, B. Keeling, et al. (1993)

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