OXIDATIVE DNA DAMAGE BY CRYSTALLINE SILICA

Using a simple DNA strand breakage assay, we detected the production o f oxidant species, probably hydroxyl free radicals, in buffered suspen sions 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 an d silica but accelerated DNA damage by silica alone and by superoxide dismutase and silica. DNA damage was blocked by catalase and by the sc avenging agents dimethyl sulfoxide and sodium benzoate. Chemical etchi ng of crystalline silica to remove impurities by treatment of the surf ace with hydrofluoric acid resulted in markedly diminished DNA damagin g ability. Even preparations of crystalline silica previously characte rized as highly pure contained trace iron impurities in amounts signif icant enough to produce oxygen free radicals in aqueous suspension. Bo th superoxide and Fenton reaction oxidants were produced. We conclude that silica is able to mediate DNA strand breakage in vitro and that t his DNA damage may be an important factor in silica toxicity.