Iron-dependent formation of 8-hydroxydeoxyguanosine in isolated DNA and mutagenicity in Salmonella typhimurium TA102 induced by crocidolite

Our plain-English summary of Iron-dependent formation of 8-hydroxydeoxyguanosine in isolated DNA and mutagenicity in Salmonella typhimurium TA102 induced by crocidolite, by S.P. Faux, P.J. Howden, L.S. Levy (Carcinogenesis, 1994).

The study

• Authors: S.P. Faux, P.J. Howden, L.S. Levy
• Journal: Carcinogenesis
• Published: 1994;15(8):1749-51
• Cited by: 35 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Treatment of isolated DNA with crocidolite asbestos significantly increased the concentration of 8-hydroxydeoxyguanosine (8-OHdG) above background. Furthermore, incubating DNA with H2O2 and crocidolite potentiated the formation of 8-OHdG above levels observed with crocidolite alone. In the presence of desferrioxamine, desferrioxamine and ferrozine, dimethylsulphoxide (DMSO) or o-phenanthroline, crocidolite-induced DNA oxidation was reduced by 36, 73, 74 and 70% respectively. Crocidolite, but not chrysotile asbestos, enhanced background revertants in Salmonella typhimurium TA102, at sub-cytotoxic concentrations in a dose-dependent manner. The mutagenic effects of crocidolite were quite small and this indicates that crocidolite was a weak mutagen in this study. The number of revertants was reduced to the spontaneous rate for this strain after the fibres had been pretreated with desferrioxamine before assaying for genotoxicity in this oxygen radical-sensitive strain. These results help to explain a mechanistic role for iron in crocidolite-induced DNA oxidation and mutagenicity in TA102.

In plain English

This short laboratory report from the University of Birmingham, UK, tested whether iron in crocidolite asbestos drives damage to genetic material. No people or animals were studied. The authors mixed isolated calf DNA with standard UICC crocidolite and measured 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxygen-radical damage to DNA. Crocidolite raised 8-OHdG 7-fold above background (P < 0.001). Adding iron-binding chemicals (desferrioxamine; desferrioxamine with ferrozine; o-phenanthroline) or the radical scavenger DMSO cut this to 4.6-, 1.9-, 2- and 1.9-fold. Crocidolite plus hydrogen peroxide raised 8-OHdG 16-fold. The authors also tested crocidolite and chrysotile on Salmonella typhimurium TA102, a bacterial strain built to detect oxidative mutation. Crocidolite increased mutant colonies with dose. Chrysotile produced only a marginal increase. At 500 micrograms per plate, the highest non-toxic crocidolite dose, the increase was 1.7-fold. This was statistically significant but below the 2-fold level of a true positive, and the authors called crocidolite a weak mutagen. Pre-treating crocidolite with desferrioxamine returned mutant counts to background. The authors concluded the results strongly suggest iron was responsible for these effects.

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, published as a short communication: isolated DNA treated with asbestos, plus a bacterial mutation test (Ames test)
• Who was studied: No human or animal subjects. Calf thymus DNA and the bacterial strain Salmonella typhimurium TA102, with three separate incubations per condition
• Exposure: UICC standard crocidolite at 5 mg/ml for the DNA experiments, with or without hydrogen peroxide, DMSO or iron chelators (desferrioxamine, ferrozine, o-phenanthroline). UICC standard crocidolite and chrysotile at 0 to 500 micrograms per plate for the bacterial test, with or without desferrioxamine pretreatment
• Main results:
  • In isolated calf thymus DNA, crocidolite increased 8-OHdG 7-fold above background (P < 0.001)
  • With desferrioxamine, desferrioxamine plus ferrozine, DMSO or o-phenanthroline, the crocidolite-induced increase was reduced to 4.6-, 1.9-, 1.9- and 2-fold above background respectively
  • Hydrogen peroxide increased 8-OHdG 16-fold above background with crocidolite and 6-fold without crocidolite
  • In TA102 bacteria, crocidolite but not chrysotile increased revertant (mutant) colonies above background in a dose-dependent manner. Crocidolite above 500 micrograms per plate was toxic to the bacteria
  • At the top sub-cytotoxic crocidolite dose (500 micrograms per plate), revertants were 1.7-fold above background. This was statistically significant (P < 0.005) but short of a true positive (2-fold). The authors described crocidolite as a weak mutagen in this study
  • Chrysotile produced only a marginal increase in revertant colonies
  • Pre-treating crocidolite with desferrioxamine reduced revertants to background level at all crocidolite concentrations tested (5 to 500 micrograms per plate)
• The authors' conclusion: The authors concluded that their results strongly suggest iron was responsible for the crocidolite-catalysed formation of 8-OHdG in isolated DNA and for the increased revertants in TA102

Topics

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

Medical terms in this study, explained in our Lexicon: Crocidolite, 8-OHdG, Chrysotile, Genotoxicity.

Related studies

• Glutathione modulates the formation of 8-hydroxydeoxyguanosine in isolated DNA and mutagenicity in Salmonella typhimurium TA100 induced by mineral fibres — P.J. Howden, S.P. Faux (1996)
• Fibre-induced lipid peroxidation leads to DNA adduct formation in Salmonella typhimurium TA104 and rat lung fibroblasts — P.J. Howden, S.P. Faux (1996)
• 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)
• Misreading of DNA templates containing 8-hydroxydeoxyguanosine at the modified base and at adjacent residues — Y. Kuchino, F. Mori, et al. (1987)
• 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)
• Induction of 8-hydroxydeoxyguanosine by man made vitreous fibres and crocidolite asbestos administered intraperitoneally in rats — C. Schürkes, W. Brock, et al. (2004)

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