Oxidative DNA damage by crystalline silica.
Using a simple DNA strand breakage assay, we detected the production of oxidant species, probably hydroxyl free radicals, in buffered suspensions of crystalline silica at pH 7.4. DNA damage was affected by the presence of oxygen and was accelerated by superoxide dismutase and by hydrogen peroxide. Deferoxamine blocked damage by hydrogen peroxide and silica but accelerated DNA damage by silica alone and by superoxide dismutase and silica. DNA damage was blocked by catalase and by the scavenging agents dimethyl sulfoxide and sodium benzoate. Chemical etching of crystalline silica to remove impurities by treatment of the surface with hydrofluoric acid resulted in markedly diminished DNA damaging ability. Even preparations of crystalline silica previously characterized as highly pure contained trace iron impurities in amounts significant enough to produce oxygen free radicals in aqueous suspension. Both superoxide and Fenton reaction oxidants were produced. We conclude that silica is able to mediate DNA strand breakage in vitro and that this DNA damage may be an important factor in silica toxicity.
Laboratory of Experimental Pathology, National Cancer Institute, Bethesda, MD 20892-0041.
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Daniel
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Y
Mao
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Saffiotti
D002374:Catalase / Q000494:pharmacology; D003460:Crystallization; D004249:DNA Damage / Q000187:drug effects*; D003676:Deferoxamine / Q000494:pharmacology; D015247:Deoxyribonuclease HindIII; D006861:Hydrogen Peroxide / Q000494:pharmacology; D010084:Oxidation-Reduction; D010100:Oxygen / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D012822:Silicon Dioxide / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000494:pharmacology
D012822:Silicon Dioxide; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D015247:Deoxyribonuclease HindIII; D003676:Deferoxamine; D010100:Oxygen