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Free Radic Biol Med. 2010 Dec 1;49(11):1685-93. doi: 10.1016/j.freeradbiomed.2010.08.031. Epub 2010 Sep 7.

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

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1
Institut für Umweltmedizinische Forschung, Heinrich-Heine-Universität, Düsseldorf, Germany.

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.

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