SILICA RADICAL-INDUCED DNA-DAMAGE AND LIPID-PEROXIDATION

In recent years, more attention has been given to the mechanism of dis ease induction caused by the surface properties of minerals. In this r espect, specific research needs to be focused on the biologic interact ions of oxygen radicals generated by mineral particles resulting in ce ll injury and DNA damage leading to fibrogenesis and carcinogenesis. I n this investigation, we used electron spin resonance (ESR) and spin t rapping to study oxygen radical generation from aqueous suspensions of freshly fractured crystalline silica. Hydroxyl radical ((OH)-O-.), su peroxide radical (O-2(.-)) and singlet oxygen (O-1(2)) were all detect ed. Superoxide dismutase (SOD) partially inhibited (OH)-O-. yield, whe reas catalase abolished (OH)-O-. generation. H2O2 enhanced (OH)-O-. ge neration while deferoxamine inhibited it, indicating that (OH)-O-. is generated via a Haber-Weiss type reaction. These spin trapping measure ments provide the first evidence that aqueous suspensions of silica pa rticles generate O-2(.-) and O-1(2). Oxygen consumption measurements i ndicate that freshly fractured silica uses molecular oxygen to generat e O-2(.-) and O-1(2). Electrophoretic assays of in vitro DNA strand br eakages showed that freshly fractured silica induced DNA strand breaka ge, which was inhibited by catalase and enhanced by H2O2. In an argon atmosphere, DNA damage was suppressed, showing that molecular oxygen i s required for the silica-induced DNA damage. incubation of freshly fr actured 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 so dium benzoate inhibited lipid peroxidation by 49, 52, and 75%, respect ively, again showing the role of oxygen radicals in silica-induced lip id peroxidation. These results show that in addition to (OH)-O-., O-2( .-) and O-1(2) may play an important role in the mechanism of silica-i nduced cellular injury.