Involvement of oxidative stress in crystalline silica-induced cytotoxicity and genotoxicity in rat alveolar macrophages

Zhuo Zhang, Han Ming Shen, Qi Feng Zhang, Choon Nam Ong

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


Alveolar macrophages (AMs) occupy a key position in silica-induced pulmonary fibrosis, although the mechanism3 are yet to be elucidated. In the present study we examined the involvement of oxidative stress and reactive oxygen species formation in silica-induced cytotoxicity and genotoxicity in cultured rat AMs. A lucigenin-dependent chemiluminescence test was used to determine superoxide anion (O2/-), and a 2',7'-dichlorofluorescin diacetate fluorescence test was employed to measure the hydrogen peroxide (H2O2) level. The cytotoxic and genotoxic effects caused by silica in AMs were examined by lactate dehydrogenase (LDH) leakage and single-cell gel electrophoresis (comet assay), respectively. The results showed that silica enhanced O2/- and H2O2 formation in AMs. There were clear dose- and time- dependent relationships in silica-induced cytotoxicity and genotoxicity. Furthermore, superoxide dismutase and catalase were able to reduce silica- induced LDH leakage and DNA damage, with concurrent significant inhibition on silica-induced oxidative stress in AMs. These findings provide convincing evidence that oxidative stress mediates the silica-induced cytotoxicity and genotoxicity. The understanding of such a mechanism may provide a scientific basis for the possible application of antioxidants in preventing the hazardous effects of silica. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)245-252
Number of pages8
JournalEnvironmental Research
Issue number3
StatePublished - Mar 2000

Bibliographical note

Funding Information:
The authors thank H. Y. Ong and Y. L. Chew for their technical support. The present study was supported by the China Medical Board (New York), Program on Environmental and Occupational Health and the Center for Environmental and Occupational Health Research, National University of Singapore. The animal study in this project was conducted in accordance with national and institutional guidelines for the protection of animal welfare.


  • Alveolar macrophage
  • Crystalline silica
  • Cytotoxicity
  • Genotoxicity
  • Oxidative stress
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biochemistry
  • General Environmental Science


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