title: Neutrophils cause oxidative DNA damage in alveolar epithelial cells.
abstract: Inflammation has been recognized as a contributing factor in the pathogenesis of some cancers. In the lung, inflammation is characterized by an influx of polymorphonuclear leukocytes (PMN) that release a variety of reactive oxygen species (ROS). The aim of the present study was to investigate the direct effect of PMN on oxidative DNA damage in lung target cells. Therefore, rat alveolar epithelial cells (RLE) were coincubated with PMN or hydrogen peroxide. Known to be correlated with the incidence of cancer, 7-hydro-8-oxo-2'deoxyguanosine (8-oxodG) was used as an effect marker for oxidative damage. Viability of the RLE, when coincubated with PMN, decreased to 43%, dependent on the ratio between PMN and RLE. After washing off PMN, 8-oxodG levels were significantly increased in RLE, but the highest levels were observed in the washed off PMN fraction. In addition, to avoid washing off procedures, immunohistochemical analysis was used to measure the 8-oxodG levels specifically in the RLE and similar results were obtained. In addition, inhibitor experiments showed that antioxidants ameliorated oxidative DNA damage. Our data provide evidence that ROS released by PMN as well as H2O2, cause oxidative DNA damage in epithelial cells.
authors.affiliation: Department of Health Risk Analysis and Toxicology, Maastricht University, The Netherlands.
authors.forename: A M
authors.initials: AM
authors.lastname: Knaapen
authors.forename: F
authors.initials: F
authors.lastname: Seiler
authors.forename: P A
authors.initials: PA
authors.lastname: Schilderman
authors.forename: P
authors.initials: P
authors.lastname: Nehls
authors.forename: J
authors.initials: J
authors.lastname: Bruch
authors.forename: R P
authors.initials: RP
authors.lastname: Schins
authors.forename: P J
authors.initials: PJ
authors.lastname: Borm
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004249:DNA Damage; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D010084:Oxidation-Reduction; D011650:Pulmonary Alveoli / Q000166:cytology / Q000473:pathology*; D051381:Rats
chemical_list: D006861:Hydrogen Peroxide