Silica radical-induced DNA damage and lipid peroxidation

In recent years, more attention has been given to the mechanism of disease induction caused by the surface properties of minerals. In this respect, specific research needs to be focused on the biologic interactions of oxygen radicals generated by mineral particles resulting in cell injury and DNA damage leading to fibrogenesis and carcinogenesis. In this investigation, we used electron spin resonance (ESR) and spin trapping to study oxygen radical generation from aqueous suspensions of freshly fractured crystalline silica. Hydroxyl radical (̇OH), superoxide radical (O₂(̇-)) and singlet oxygen (¹O₂) were all detected. Superoxide dismutase (SOD) partially inhibited ̇OH yield, whereas catalase abolished OH generation. H₂O₂ enhanced ̇OH generation while deferoxamine inhibited it, indicating that ̇OH is generated via a Haber-Weiss type reaction. These spin trapping measurements provide the first evidence that aqueous suspensions of silica particles generate O₂(̇-) and ¹O₂. Oxygen consumption measurements indicate that freshly fractured silica uses molecular oxygen to generate O₂(̇-) and ¹O₂. Electrophoretic assays of in vitro DNA strand breakages showed that freshly fractured silica induced DNA strand breakage, which was inhibited by catalase and enhanced by H₂O₂. In an argon atmosphere, DNA damage was suppressed, showing that molecular oxygen is required for the silica-induced DNA damage. Incubation of freshly fractured silica with linoleic acid generated linoleic acid-derived free radicals and caused dose-dependent lipid peroxidation as measured by ESR spin trapping and malondialdehyde formation. SOD, catalase, and sodium benzoate inhibited lipid peroxidation by 49, 52, and 75%, respectively, again showing the role of oxygen radicals in silica-induced lipid peroxidation. These results show that in addition to ̇OH, O₂(̇-) and ¹O₂ may play an important role in the mechanism of silica-induced cellular injury.