Glutathione modulates the formation of 8-hydroxydeoxyguanosine in isolated DNA and mutagenicity in Salmonella typhimurium TA100 induced by mineral fibres.
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.
Howden
P J
PJ
Institute of Occupational Health, University of Birmingham, Edgbaston, UK.
Faux
S P
SP
D000080242:8-Hydroxy-2'-Deoxyguanosine; D017638:Asbestos, Crocidolite; D018736:DNA Adducts / Q000378:metabolism*; D004269:DNA, Bacterial / Q000378:metabolism*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D019016:Mineral Fibers; D009152:Mutagenicity Tests; D009153:Mutagens; D010084:Oxidation-Reduction; D012486:Salmonella typhimurium
D018736:DNA Adducts; D004269:DNA, Bacterial; D019016:Mineral Fibers; D009153:Mutagens; D017638:Asbestos, Crocidolite; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D005978:Glutathione