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Mechanisms of neutrophil-induced DNA damage in respiratory tract epithelial cells

  • Ad. M. Knaapen
  • Roel P. F. Schins
  • Dünya Polat
  • Andrea Becker
  • Paul J. A. Borm
Chapter
Part of the Developments in Molecular and Cellular Biochemistry book series (DMCB, volume 37)

Abstract

Reactive oxygen species (ROS) released by neutrophils have been suggested to play an important role in cancer development. Since the mechanisms underlying this effect in the respiratory tract are still unclear, we evaluated DNA damage induced by neutrophils in respiratory tract epithelial cellsin vitroandin vivo.Forin vitrostudies, rat lung epithelial cells (RLE) were co-incubated with activated neutrophils, neutrophil-conditioned medium, or hydrogen peroxide. Forin vivostudies, we considered the human nose as a target organ, comparing neutrophilic inflammation in the nasal lavage fluid with the oxidative DNA lesion 8-hydroxydeoxyguanosine (8-OHdG) in epithelial cells obtained by nasal brush. Ourin vitrodata show that human neutrophils are able to induce both 8-OHdG and strand breaks in DNA from RLE cells. Our data also suggest that DNA damage induced by neutrophils is inhibited when neutrophil-derived H2O2is consumed by myeloperoxidase. In contrast, in the nose no association between neutrophil numbers and 8-OHdG was found. Therefore, it remains unclear whether neutrophils pose a direct genotoxic risk for the respiratory tract epithelium during inflammation, and morein vivostudies are needed to elucidate the possible association between neutrophils and genotoxicity in the lung. (Mol Cell Biochem 234/235: 143–151, 2002)

Key words

DNA damage genotoxicity 8-hydroxydeoxyguanosine inflammation nasal brush nasal lavage neutrophils reactive oxygen species respiratory tract epithelial cells strand breaks 

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Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Ad. M. Knaapen
    • 1
  • Roel P. F. Schins
    • 1
  • Dünya Polat
    • 1
  • Andrea Becker
    • 1
  • Paul J. A. Borm
    • 1
  1. 1.Particle Research CoreInstitute for Environmental Health (IUF)DüsseldorfGermany

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