SHORT COMMUNICATION: Glutathione modulates the formation of 8-hydroxydeoxyguannosine in isolated DNA and mutagenicity in Salmonella typhimurium TA100 induced by mineral fibres

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.

The molecular basis of asbestos induced lung injury

“…Whether or not reduced glutathione (GSH) protects against asbestos induced DNA damage is also unclear. Crocidolite induced 8-OHdG formation caused a 3–4 fold increase in mutagenicity in Salmonella typhimurium and these effects were prevented by GSH 97. In contrast, we found that liposomal GSH and N-acetyl- l -cysteine (NAC), a reducing agent and glutathione precursor, did not prevent asbestos induced DNA-SB formation in A549 cells as assessed by alkaline elution 98.…”

DNA Damage by tert-Butoxyl Radicals Generated in the Photolysis of a Water-Soluble, DNA-Binding Peroxyester Acting as a Radical Source

“…That radicals are, indeed, the active species in these DNA oxidations was confirmed by inhibition (cf. Results) with the radical scavenger di- tert -butylcresol ( , ) or the hydrogen donor glutathione ( , ). Furthermore, photosensitization reactions by the arene chromophore do not play a significant role, as was shown by the lack of DNA damage when the samples were irradiated in the presence of ester 2 .…”

Genotoxic Mechanisms of Asbestos Fibers: Role of Extranuclear Targets

“…In the past few years, several mutagenicity assays that are proficient in detecting either large deletions, homologous recombinations, or score mutants located on nonessential genes have been used successfully to demonstrate the mutagenic potential of various fiber types, suggesting a close relationship between chromosomal abnormalities that have occurred frequently in humans and rodent cells exposed to fibers and carcinogenicity in vivo ( − ). Furthermore, there is evidence that phagocytotic uptake of fibers plays an essential role in mediating asbestos toxicity and that fiber-mediated mutation yield in mammalian cells can be enhanced by buthionine-SR-sulfoximine, a competitive inhibitor of the enzyme γ-glutamyl cysteine synthetase, and can be inhibited by concurrent treatment with catalase and superoxide dismutase (SOD) ( − ). These findings indicate that oxyradicals may be the key determinants in asbestos-induced mutagenesis and carcinogenesis.…”