Silica Radical-Induced DNA Damage and Lipid Peroxidation

Abstract

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 (0OH), superoxide radical (02-) and singlet oxygen (102) were all detected. Superoxide dismutase (SOD) partially inhibited *OH yield, whereas catalase abolished 0OH generation. H202 enhanced 0OH 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 O-and 10 Oxygen consumption measurements indicate that freshly fractured silica uses molecular oxygen to generate 02-and 10 . 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 H202. 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, 0°and 102 may play an important role in the mechanism of silica-induced cellular injury. -Environ Health Perspect 102(Suppl 10):149-154 (1994)

Silica binding and toxicity in alveolar macrophages

“…In studies with artificial crystalline silica, the amount of exposed surface and size/shape of the particle also influenced cytotoxic potential [80]. Evidence strongly suggests that silica-derived ROS is directly responsible for in vitro DNA damage [81][82][83], various morphological changes including apoptosis in in vitro cell cultures [79,84,85], and acute lung damage in vivo [71]. The DNA damage is caused primarily by the hydroxyl radical, which is the by-product of iron contaminated silica [86].…”

Involvement of protein kinase C in crystalline silica-induced activation of the MAP kinase and AP-1 pathway

“…Increasing evidence from epidemiological and animal studies has also implicated crystalline silica as a potential carcinogen (3,28,32,47). For example, inhalation of silica has been shown to cause lung tumors in rats (27)(28)(29)33).…”

Induction of Activator Protein-1 through Reactive Oxygen Species by Crystalline Silica in JB6 Cells

“…Previous studies have shown that silica causes direct DNA damage and mammalian cell transformation (10,11). Earlier studies have also demonstrated that FFSi 1 is capable of generating hydroxyl radicals ( ⅐ OH) upon reaction with aqueous media (12)(13)(14).…”

“…The silicon-based free radicals (Si ⅐ , SiO ⅐ , and SiOO ⅐ ) and the associated generation of H 2 O 2 and ⅐ OH appear to be involved in the lipid peroxidation and membrane damage (12)(13)(14)(15). These radicals are also associated with silica-induced DNA damage, for example both strand breakage and hydroxylation of dG residues have been observed (10,17). O 2 .…”