Fibre-induced lipid peroxidation leads to DNA adduct formation in Salmonella typhimurium TA104 and rat lung fibroblasts.
Certain end-products of lipid peroxidation bind to DNA forming a fluorescent chromophore. Incubation of both Salmonella typhimurium TA104 and a rat lung fibroblast cell line, RFL-6, with various types of mineral fibre resulted in a time- and dose-dependent increase in DNA fluorescence. The increase in DNA fluorescence was shown to be directly related to the amount of iron that could be mobilized from the fibre surface using in vitro studies in the absence of cells or bacteria. Crocidolite and man-made vitreous fibre-21 (MMVF-21) mobilized significant quantities of iron and were significantly more active than chrysotile and refactory ceramic fibre-1 (RCF-1). Fibre-induced malondialdehyde-DNA adduct formation, the fluorescent product, was increased by incubating cells with buthionine sulfoximine and ameliorated by co-treatment with N-acetylcysteine, indicating a protective role for glutathione. Similarly, vitamin E was also shown to inhibit DNA adduct formation. These results suggest that mineral fibre-induced lipid peroxidation produced genotoxic products which can diffuse into nucleus and interact with cellular DNA. In conclusion, fibre-induced lipid peroxidation may be a possible mechanism in the genotoxic action of fibrous materials.
Howden
P J
PJ
Institute of Occupational Health, University of Birmingham, UK.
Faux
S P
SP
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000931:Antidotes / Q000494:pharmacology; D017638:Asbestos, Crocidolite / Q000633:toxicity*; D017632:Asbestos, Serpentine / Q000633:toxicity*; D019328:Buthionine Sulfoximine; D002273:Carcinogens / Q000633:toxicity*; D004247:DNA / Q000378:metabolism; D018736:DNA Adducts / Q000096:biosynthesis*; D003676:Deferoxamine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005297:Ferrozine / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism*; D005898:Glass; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation; D008168:Lung / Q000166:cytology; D008315:Malondialdehyde / Q000378:metabolism; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D019016:Mineral Fibers / Q000633:toxicity; D051381:Rats; D012486:Salmonella typhimurium / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000931:Antidotes; D017632:Asbestos, Serpentine; D002273:Carcinogens; D018736:DNA Adducts; D004791:Enzyme Inhibitors; D019016:Mineral Fibers; D017392:Thiobarbituric Acid Reactive Substances; D017638:Asbestos, Crocidolite; D008717:Methionine Sulfoximine; D005297:Ferrozine; D008315:Malondialdehyde; D019328:Buthionine Sulfoximine; D004247:DNA; D005978:Glutathione; D003676:Deferoxamine; D000111:Acetylcysteine