Mechanisms of neutrophil-induced DNA damage in respiratory tract epithelial cells.
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 cells in vitro and in vivo. For in vitro studies, rat lung epithelial cells (RLE) were co-incubated with activated neutrophils, neutrophil-conditioned medium, or hydrogen peroxide. For in vivo studies, 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. Our in vitro data 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 H2O2 is 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, andmore in vivo studies are needed to elucidate the possible association between neutrophils and genotoxicity in the lung.
Knaapen
Ad M
AM
Particle Research Core, Institute for Environmental Health (IUF), Düsseldorf, Germany.
Schins
Roel P F
RP
Polat
Dünya
D
Becker
Andrea
A
Borm
Paul J A
PJ
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002648:Child; D018920:Coculture Techniques; D020552:Comet Assay; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009504:Neutrophils / Q000201:enzymology / Q000378:metabolism*; D018384:Oxidative Stress; D051381:Rats; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*
D017077:Culture Media, Conditioned; D000080242:8-Hydroxy-2'-Deoxyguanosine; D006861:Hydrogen Peroxide; D003849:Deoxyguanosine