The role of catalytic iron in asbestos induced lipid peroxidation and DNA-strand breakage in C3H10T1/2 cells

Our plain-English summary of The role of catalytic iron in asbestos induced lipid peroxidation and DNA-strand breakage in C3H10T1/2 cells, by C.J. Turver, R.C. Brown (British Journal of Cancer, 1987).

The study

• Authors: C.J. Turver, R.C. Brown
• Journal: British Journal of Cancer
• Published: 1987;56(2):133-6
• Cited by: 67 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The involvement of catalytic iron in the vitro activities of crocidolite asbestos has been investigated. Exposure of C3H10T1/2 cells to either the UICC crocidolite standard reference sample or a non fibrous (milled) derivative resulted in an increase of thiobarbituric acid reactive substances. This catalytic activity was inhibited by pretreatment with the iron chelator desferrioxamine. The effect of this activity on cellular DNA was measured in an assay based on the production of DNA-strand breaks. Increased levels of DNA-strand breaks were detected in cultures treated with both the milled and UICC crocidolite. Inclusion of desferrioxamine with the asbestos inhibited DNA-strand breakage. It is concluded the catalytic iron present on the dust is capable of damaging both lipid and DNA and that this could be an important mechanism in asbestos pathogenicity.

In plain English

In this laboratory study, the authors exposed cultured C3H10T1/2 cells (a mouse embryo cell line, according to a reference the authors cite) to crocidolite asbestos. They used the UICC crocidolite reference sample and a ball-milled, non-fibrous version, with and without desferrioxamine, an iron-binding drug. Crocidolite increased thiobarbituric acid reactive substances (TBARS), a sign of oxidative damage to fats. Desferrioxamine significantly reduced TBARS in both asbestos-treated and control cultures. Milled crocidolite was at least as effective as the original sample. After 2.5 hours neither dust significantly increased DNA-strand breaks; after 24 hours all concentrations did. DNA damage was measured as the percentage of labelled DNA released after enzyme treatment. Mean release was 63.20% for crocidolite and 70.45% for milled crocidolite, each at 200 micrograms per square centimetre, against 34.04% for untreated controls. With desferrioxamine these were 51.61%, 52.37% and 16.07%; the authors called the reduction in asbestos-induced breakage only small. In medium with no added iron, desferrioxamine significantly inhibited strand breaks. The authors concluded that asbestos can cause DNA damage by an iron-dependent mechanism, and that these effects did not depend on fibre size.

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) cell culture experiment
• Who was studied: cultured cells of the C3H10T1/2 cell line, described in a cited reference as a cloned line of C3H mouse embryo cells; no humans or animals were studied
• Exposure: UICC crocidolite asbestos and a sample of it ball-milled for 8 hours into a low-cytotoxicity, non-fibrous dust, at doses up to 200 micrograms per square centimetre of growth area for 2.5 or 24 hours, with or without 300 micromolar desferrioxamine (an iron chelator)
• Main results:
  • Crocidolite increased the accumulation of TBARS (a measure of lipid peroxidation) in the cell cultures
  • Desferrioxamine significantly reduced TBARS formation in both asbestos-treated and control cultures
  • Milled (non-fibrous) crocidolite was at least as effective as the UICC sample in producing TBARS
  • After only 2.5 hours of exposure, neither milled nor UICC crocidolite significantly increased DNA-strand breaks
  • After 24 hours of exposure, all concentrations produced significant DNA-strand breakage compared with the control
  • DNA-strand breakage was measured as the percentage of radioactive label released from the nitrocellulose filter by nuclease treatment
  • Untreated control cultures (no dust): mean 34.04 percent plus or minus 9.73 (6 determinations) of label released without desferrioxamine, and 16.07 percent plus or minus 4.21 (6) with 300 micromolar desferrioxamine
  • Crocidolite at 200 micrograms per square centimetre: mean 63.20 percent plus or minus 7.79 (5 determinations) of label released without desferrioxamine, and 51.61 percent plus or minus 10.95 (4) with desferrioxamine
  • Milled crocidolite at 200 micrograms per square centimetre: mean 70.45 percent plus or minus 8.38 (5 determinations) of label released without desferrioxamine, and 52.37 percent plus or minus 1.75 (5) with desferrioxamine
  • In the first experiment, in DMEM medium, the reduction in asbestos-induced DNA-strand breakage with desferrioxamine was only small
  • In a second experiment in MEM medium with no added iron, desferrioxamine produced significant inhibition of asbestos-induced DNA-strand breaks
  • The positive control chemical 4-nitroquinoline-1-oxide caused DNA-strand breaks in a dose-dependent manner, which the authors took as confirming that the test worked
• The authors' conclusion: The authors concluded that asbestos can cause DNA damage by a mechanism that depends on the presence of iron, consistent with a free-radical mechanism. They also wrote that these effects were not fibre-size dependent but may still represent an important mechanism in the causation of asbestos-associated disease.
• Limitations the authors state:
  • The authors noted that iron present in the DMEM culture medium could have reduced the effectiveness of desferrioxamine in the first DNA experiment. They ran a second experiment in iron-free MEM medium to address this.

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, UICC.

Related studies

• Lipid peroxidation in microsomes induced by crocidolite fibres — M. Gulumian, F. Sardianos, et al. (1983)
• Crocidolite-induced lipid peroxidation in rat lung microsomes. I. Role of different ions — M. Gulumian, T.A. Kilroe-Smith (1987)
• Interrelationship between hemolysis and lipid peroxidation of human erythrocytes induced by silicic acid and silicate dusts — S.V. Singh, Q. Rahman (1987)
• The stimulatory effects of asbestos on NADPH-dependent lipid peroxidation in rat liver microsomes — M. Fontecave, D. Mansuy, et al. (1987)
• Microsomal lipid peroxidation and oxy-radicals formation are induced by insoluble iron-containing minerals — M. Fontecave, M. Jaouen, et al. (1990)
• SV40 oncoproteins enhance asbestos-induced DNA double-strand breaks and abrogate senescence in murine mesothelial cells — J.R. Pietruska, A.B. Kane (2007)

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