Generation of free radicals from freshly fractured silica dust. Potential role in acute silica-induced lung injury

Data presented here indicate that freshly fractured silica exhibits surface characteristics and biologic reactivity distinct from aged silica, and on this basis we propose that these surface features may lead to enhanced manifestations of lung injury. Grinding of silica produces ~10¹⁰ Ṡi and Si-Ȯ (silicon-based) radicals per gram of dust on the particulate surface which are characterized by an electron spin resonance (ESR) spectrum centered around g = 2.0015. These silicon-based radicals react with aqueous media to produce ȮH radicals, which are demonstrable using a DMPO spin trap. The concentration of silicon-based radicals in silica decreases with aging in air and exhibits a half-life of ~30 h, whereas its ability to generate ȮH radicals in aqueous solution decreases with a half-life of ~20 h. However, on storage in aqueous media, the concentration of silicon-based radicals and the dust's ability to generate ȮH radicals decrease significantly within a few minutes. Freshly ground silica is also more biologically reactive than aged silica, because freshly crushed silica activates a greater respiratory burst in alveolar macrophages than aged silica, i.e., storage of ground dust in air decreases silica-induced superoxide anion secretion, hydrogen peroxide release, and NBT reduction by 25%, 68%, and 43%, respectively. Furthermore, compared to aged silica, freshly ground silica exhibits a greater cytotoxic effect on cellular membrane integrity, i.e., a 1.5-fold increase in LDH release from macrophages, a 36-fold increase in hemolytic activity, and a three-fold increase in the ability to induce lipid peroxidation. Because acute silicosis is frequently associated with occupations in which freshly fractured crystalline silica of respirable size is generated, the present study suggests that fracture-generated silicon-based radicals may play a significant role in the pathogenesis of this disease.