Silica radical-induced DNA damage and lipid peroxidation.
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)
Shi
X
X
Laboratory of Experimental Pathology, National Cancer Institute, Bethesda, Maryland 20892.
Mao
Y
Y
Daniel
L N
LN
Saffiotti
U
U
Dalal
N S
NS
Vallyathan
V
V
D004249:DNA Damage; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D006861:Hydrogen Peroxide / Q000494:pharmacology; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology; D008054:Lipid Peroxides / Q000378:metabolism*; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism; D012822:Silicon Dioxide / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism
D005609:Free Radicals; D008041:Linoleic Acids; D008054:Lipid Peroxides; D013481:Superoxides; D012822:Silicon Dioxide; D019787:Linoleic Acid; D006861:Hydrogen Peroxide; D010100:Oxygen