Silica radical-induced DNA damage and lipid peroxidation.
Shi-X; Mao-Y; Daniel-LN; Saffiotti-U; Dalal-NS; Vallyathan-V
Environ Health Perspect 1994 Dec; 102(Suppl 10):149-154
An effort was made to determine the generation of superoxide radicals by an aqueous silica (14808607) particle suspension, formation of singlet oxygen by freshly fractured silica, the role of free oxygen radicals in DNA damage and lipid peroxidation, and the possible dependence of silica induced DNA damage on molecular oxygen. Electron spin resonance (ESR) and spin trapping was used to detect oxygen radical generation from aqueous suspensions of freshly fractured crystalline silica. DNA strand breakage assays were performed. Measurements were taken of oxygen consumption and lipid peroxidation. Superoxide radicals and singlet oxygen were detected in the aqueous suspensions of freshly fractured silica by ESR. Aqueous suspensions of freshly fractured silica were observed to cause DNA double strand breakage via oxygen dependent, free radical mediated reactions. Freshly fractured silica was also shown to cause lipid peroxidation and generate lipid derived free radicals, which were prevented by oxygen radical scavengers. DNA damage was suppressed in an argon atmosphere, demonstrating the requirement for molecular oxygen. The role of oxygen radicals in silica induced lipid peroxidation was suggested by the 49, 52, and 75% inhibition of lipid peroxidation by superoxide-dismutase, catalase, and sodium- benzoate, respectively. The authors conclude that the superoxide- radical and singlet oxygen, as well as the hydroxyl radical, are important in the mechanism of silica induced cell injury.
NIOSH-Author; Free-radical-generation; Silica-dusts; Genotoxic-effects; Oxidative-processes; Cytotoxic-effects; Cell-damage; DNA-damage; Enzymatic-effects;
Author Keywords: silica-based radicals; hydroxyl radical; singlet oxygen; superoxide radical; DNA damage; lipid peroxidation; electron spin resonanace; spin trapping; crystalline silica; silicosis; carcinogenesis
Xianglin Shi, Laboratory of Experimental Pathology, National Cancer Institute, Building 41, Room C301, Bethesda, MD 20892
Environmental Health Perspectives