title: Neutrophil-derived ROS contribute to oxidative DNA damage induction by quartz particles.
abstract: The carcinogenicity of respirable quartz is considered to be driven by reactive oxygen species (ROS) generation in association with chronic inflammation. The contribution of phagocyte-derived ROS to inflammation, oxidative stress, and DNA damage responses was investigated in the lungs of C57BL/6J wild-type and p47(phox-/-) mice, 24h after pharyngeal aspiration of DQ12 quartz (100 mg/kg bw). Bone-marrow-derived neutrophils from wild-type and p47(phox-/-) mice were used for parallel in vitro investigations in coculture with A549 human alveolar epithelial cells. Quartz induced a marked neutrophil influx in both wild-type and p47(phox-/-) mouse lungs. Significant increases in mRNA expression of the oxidative stress markers HO-1 and γ-GCS were observed only in quartz-treated wild-type animals. Oxidative DNA damage in lung tissue was not affected by quartz exposure and did not differ between p47(phox-/-) and WT mice. Differences in mRNA expression of the DNA repair genes OGG1, APE-1, DNA Polβ, and XRCC1 were also absent. Quartz treatment of cocultures containing wild-type neutrophils, but not p47(phox-/-) neutrophils, caused increased oxidative DNA damage in epithelial cells. Our study demonstrates that neutrophil-derived ROS significantly contribute to pulmonary oxidative stress responses after acute quartz exposure, yet their role in the associated induction of oxidative DNA damage could be shown only in vitro.
authors.affiliation: Institut für Umweltmedizinische Forschung, Heinrich-Heine-Universität, Düsseldorf, Germany.
authors.forename: Damien
authors.initials: D
authors.lastname: van Berlo
authors.forename: Anton
authors.initials: A
authors.lastname: Wessels
authors.forename: Agnes W
authors.initials: AW
authors.lastname: Boots
authors.forename: Verena
authors.initials: V
authors.lastname: Wilhelmi
authors.forename: Agnes M
authors.initials: AM
authors.lastname: Scherbart
authors.forename: Kirsten
authors.initials: K
authors.lastname: Gerloff
authors.forename: Frederik J
authors.initials: FJ
authors.lastname: van Schooten
authors.forename: Catrin
authors.initials: C
authors.lastname: Albrecht
authors.forename: Roel P F
authors.initials: RP
authors.lastname: Schins
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D053758:Nanoparticles / Q000009:adverse effects; D009504:Neutrophils / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D011014:Pneumonia / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011791:Quartz / Q000009:adverse effects*; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D017382:Reactive Oxygen Species; D011791:Quartz; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1