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Oxidative DNA damage by crystalline silica
L N Daniel1, Y Mao, U Saffiotti
1Laboratory of Experimental Pathology, National Cancer Institute, Bethesda, MD 20892-0041.
Free Radical Biology & Medicine
|May 1, 1993
Summary
Crystalline silica generates oxidant species, causing DNA strand breaks in vitro. This silica-mediated DNA damage may contribute to its toxicity.
Area of Science:
- Toxicology
- Biochemistry
- Materials Science
Background:
- Crystalline silica exposure is linked to various health issues.
- The precise mechanisms underlying silica toxicity are not fully understood.
- Oxidative stress is implicated in the pathogenesis of silica-related diseases.
Purpose of the Study:
- To investigate the ability of crystalline silica to induce DNA damage in vitro.
- To identify the specific oxidant species responsible for silica-induced DNA damage.
- To explore the role of impurities, particularly iron, in mediating silica's genotoxic effects.
Main Methods:
- A DNA strand breakage assay was employed using buffered suspensions of crystalline silica at pH 7.4.
- The effects of oxygen, superoxide dismutase, hydrogen peroxide, deferoxamine, catalase, dimethyl sulfoxide, and sodium benzoate on DNA damage were assessed.
- Chemical etching with hydrofluoric acid was used to remove surface impurities from silica preparations.
- Trace iron content in silica samples was quantified.
Main Results:
- Crystalline silica produced oxidant species, likely hydroxyl free radicals, in aqueous suspension.
- DNA damage was dependent on oxygen presence and was potentiated by superoxide dismutase and hydrogen peroxide.
- Deferoxamine exhibited differential effects, blocking some damage while accelerating others.
- Catalase and radical scavenging agents inhibited DNA damage.
- Surface etching significantly reduced the DNA damaging potential of silica.
- Even highly pure silica contained significant iron impurities capable of generating oxygen free radicals via Fenton reactions.
Conclusions:
- Crystalline silica can mediate DNA strand breakage in vitro.
- The production of superoxide and Fenton reaction oxidants contributes to silica's genotoxicity.
- Trace iron impurities play a critical role in the generation of reactive oxygen species by silica.
- Silica-mediated DNA damage is a potential key factor in silica toxicity.