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 (.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.(ABSTRACT TRUNCATED AT 250 WORDS)ImagesFigure 7.

Airway Delivery of Silica Increases Susceptibility to Mycobacterial Infection in Mice: Potential Role of Repopulating Macrophages

“…Silica has also been shown to disrupt calcium homeostasis (23), increase oxygen radical production, and induce DNA damage in AMs (24, 25). At high concentrations in vitro, silica is directly toxic to AMs resulting in cell injury or death (21, 26).…”

The Sources of Inflammatory Mediators in the Lung after Silica Exposure

“…Silica can cause direct DNA damage and mammalian cell transformation (Daniel et al 1995; Shi et al 1994). The initial event, however, is an inflammatory response, including oxidant production and recruitment of inflammatory cells into the lung.…”

Evaluation of serum and urinary neopterin levels as a biomarker for occupational exposure to crystalline silica

“…Silica dust trigger producing ROS from alveolar macrophages, which overwhelms antioxidant defenses of the lung and contribute to lipid peroxidation and an increased likelihood of lung injury and DNA damage. [282930] Therefore, in some studies, plasma/serum malondialdehyde levels as an index of lipid peroxidation, 8-hydroxyldeoxyguanosine as an oxidative stress marker, and erythrocyte reduced glutathione levels as an index of antioxidant status were investigated in silica-exposed participants. [282930] Moreover, more attention has been given to assay of in-vitro DNA strand breakages resulting from the biologic interactions of oxygen radicals generated by silica particles.…”

“…[282930] Therefore, in some studies, plasma/serum malondialdehyde levels as an index of lipid peroxidation, 8-hydroxyldeoxyguanosine as an oxidative stress marker, and erythrocyte reduced glutathione levels as an index of antioxidant status were investigated in silica-exposed participants. [282930] Moreover, more attention has been given to assay of in-vitro DNA strand breakages resulting from the biologic interactions of oxygen radicals generated by silica particles. [3031] Gulumian et al .…”

“…[282930] Moreover, more attention has been given to assay of in-vitro DNA strand breakages resulting from the biologic interactions of oxygen radicals generated by silica particles. [3031] Gulumian et al . (2006) performed a comprehensive review on suitable biomarkers of silicosis and coal worker's pneumoconiosis and introduced the number of ideal biological markers of them.…”