Neutrophil-derived ROS contribute to oxidative DNA damage induction by quartz particles

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/6 J w...

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Bibliographic Details
Published in:Free radical biology & medicine 2010-12, Vol.49 (11), p.1685-1693
Main Authors: van Berlo, Damien, Wessels, Anton, Boots, Agnes W., Wilhelmi, Verena, Scherbart, Agnes M., Gerloff, Kirsten, van Schooten, Frederik J., Albrecht, Catrin, Schins, Roel P.F.
Format: Article
Language:English
Subjects:
Alveoli
Animals
Cells, Cultured
Coculture Techniques
DNA Damage
DNA Repair - drug effects
DNA Repair - genetics
Free radicals
Humans
Mice
Mice, Inbred C57BL
Mice, Knockout
NADPH oxidase
NADPH Oxidases - genetics
NADPH Oxidases - metabolism
Nanoparticles - adverse effects
Neutrophil
Neutrophils - metabolism
Oxidative DNA damage
Oxidative Stress - drug effects
Pneumonia - etiology
Pneumonia - genetics
Pneumonia - metabolism
Pneumonia - pathology
Quartz
Quartz - adverse effects
Reactive Oxygen Species - metabolism
Reactive Oxygen Species - pharmacology
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Summary: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/6 J wild-type and p47 phox−/− mice, 24 h 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.
ISSN:0891-5849
1873-4596
DOI:10.1016/j.freeradbiomed.2010.08.031