Glutathione modulates the formation of 8-hydroxydeoxyguanosine in isolated DNA and mutagenicity in Salmonella typhimurium TA100 induced by mineral fibres

Our plain-English summary of Glutathione modulates the formation of 8-hydroxydeoxyguanosine in isolated DNA and mutagenicity in Salmonella typhimurium TA100 induced by mineral fibres, by P.J. Howden, S.P. Faux (Carcinogenesis, 1996).

The study

• Authors: P.J. Howden, S.P. Faux
• Journal: Carcinogenesis
• Published: 1996;17(10):2275-7
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Treatment of isolated DNA with crocidolite and man-made vitreous fibre-21 (MMVF-21) significantly increased the concentration of 8-hydroxydeoxyguanosine (8-OHdG) in isolated DNA above background levels and co-treatment with glutathione (GSH) eliminated this effect. Crocidolite, MMVF-21 and chrysotile fibres increased the number of revertants in Salmonella typhimurium TA100 and GSH-deficient strains, TA100/NG-54 and TA100/NG-57, over background levels. This increase was small in TA100 but was greater in the GSH-deficient strains. When these bacterial strains were further depleted of GSH by co-culture with buthionine sulfoximine, all fibres tested caused a significant increase in the number of revertants over the parent strains. Pre-treatment with the GSH precursor N-acetyl-L-cysteine reduced the number of revertants to below that of the parent strain. Previous studies have shown a mechanistic role for iron-catalyzed production of oxygen radicals in the mutagenicity of fibres and this study suggests a protective role for GSH against such oxidative damage possibly by acting as a radical scavenger.

In plain English

This short laboratory report tested whether glutathione (GSH), a natural antioxidant found in cells, protects against damage caused by mineral fibres. It studied isolated DNA and bacteria, not people or animals. The authors exposed calf thymus DNA to UICC crocidolite asbestos or a man-made vitreous fibre (MMVF-21), with hydrogen peroxide present. They measured 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative DNA damage. Crocidolite raised 8-OHdG about 5-fold and MMVF-21 about 6-fold above background. Adding GSH reduced levels to below background. The authors also tested crocidolite, chrysotile and MMVF-21 on Salmonella typhimurium TA100 bacteria and on two strains with lower GSH, at 41 and 32% of the parent strain's level. The number of mutated bacteria (revertants) was low in TA100 and slightly higher in the two lower-GSH strains. Lowering GSH with buthionine sulfoximine significantly increased revertants over the parent strain in all strains. Raising GSH with N-acetyl-L-cysteine brought revertants below the parent strains' levels. The authors concluded that the results strongly suggest GSH protects these bacteria against iron-mediated oxidative damage and mutagenicity from these fibres.

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 was treated with fibres and oxidative DNA damage (8-OHdG) was measured. Bacteria were tested for mutations using the plate incorporation assay.
• Who was studied: Isolated calf thymus DNA. Salmonella typhimurium strain TA100 and two glutathione-deficient strains, TA100/NG54 and TA100/NG57. Work was done at the Institute of Occupational Health, University of Birmingham, UK.
• Exposure: Fibres tested: UICC crocidolite asbestos, UICC chrysotile asbestos (bacteria only) and the man-made vitreous fibre MMVF-21. DNA was incubated with fibres in the presence of hydrogen peroxide (1 mM) for 5 hours at 37°C. Bacteria received fibres at 5 to 500 micrograms per plate. Glutathione was varied in three ways: by adding GSH (2 mM) to the DNA incubations, by lowering it in bacteria with buthionine sulfoximine (BSO, 1 mM), and by raising it in bacteria with N-acetyl-L-cysteine (NAC, 5 mM).
• Main results:
  • In isolated DNA, crocidolite increased 8-OHdG about 5-fold and MMVF-21 about 6-fold above background levels (P less than 0.05).
  • In isolated DNA, adding GSH reduced 8-OHdG formation to below background levels (P less than 0.05).
  • Strains TA100/NG54 and TA100/NG57 had significantly lower GSH than the parent strain TA100: 41% and 32% of its level, respectively.
  • Without BSO or NAC pre-treatment, the revertant rate was low in TA100 and slightly higher in the lower-GSH strains TA100/NG54 and TA100/NG57. The authors described this as correlating with relative GSH content.
  • In all strains, lowering GSH with BSO before fibre treatment significantly increased revertants over the parent strain (P less than 0.05).
  • Raising GSH with NAC, alone or with BSO, reduced revertants to below the levels of the parent strains.
• The authors' conclusion: The authors concluded that the results strongly suggest GSH plays a protective role against iron-mediated oxidative damage and mutagenicity caused by crocidolite, MMVF-21 and chrysotile fibres in S. typhimurium TA100.

Topics

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

Medical terms in this study, explained in our Lexicon: Glutathione (GSH), Crocidolite, Vitreous, 8-OHdG, Chrysotile.

Related studies

• Iron-dependent formation of 8-hydroxydeoxyguanosine in isolated DNA and mutagenicity in Salmonella typhimurium TA102 induced by crocidolite — S.P. Faux, P.J. Howden, et al. (1994)
• Fibre-induced lipid peroxidation leads to DNA adduct formation in Salmonella typhimurium TA104 and rat lung fibroblasts — P.J. Howden, S.P. Faux (1996)
• Formation of 8-hydroxydeoxyguanosine by asbestos and man made mineral fibres — P. Leanderson, P. Söderkvist, et al. (1988)
• 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)
• Determination of carcinogenic potential of mineral fibers by 8-hydroxydeoxyguanosine as a marker of oxidative DNA damage in mammalian cells — N. Murata-Kamiya, T. Tsutsui, et al. (1997)
• Inhaled crocidolite mutagenicity in lung DNA — B. Rihn, C. Coulais, et al. (2000)

Browse more research in Carcinogenesis, or return to medical research.