Dokument: Mechanisms of genotoxicity of inhalable particles: in vitro & in vivo investigations
| Titel: | Mechanisms of genotoxicity of inhalable particles: in vitro & in vivo investigations | |||||||
| Weiterer Titel: | Mechanismen der Genotoxizität von inhalierbaren Partikeln: in vitro & in vivo Untersuchungen | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=13934 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20100127-145445-0 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Dipl. Biol. Wessels, Anton [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Dr. Proksch Peter [Gutachter] Prof. Dr. Wätjen, Wim [Gutachter] | |||||||
| Stichwörter: | Toxicology, Particle Research, Genotoxicity, Inflammation | |||||||
| Dewey Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik » 570 Biowissenschaften; Biologie | |||||||
| Beschreibung: | The aim of this thesis was to elucidate the mechanisms leading to oxidative DNA damage after particle exposure. In this regard one has to distinguish between primary (particle-driven) and secondary (inflammation-driven) genotoxicity. Three independent studies were performed, which were different in the choice of particulate matter and experimental set-up.
In study 1 the human lung epithelial cell line A549 was exposed to size-fractionated ambient PM samples, collected from locations with contrasting traffic profiles. Significant differences were found in oxidant-generating capacity, cytotoxicity, interleukin-8 release and oxidative DNA damage. Effects were found to depend more on the sampling site than on the size fraction. The data confirm that traffic is an important factor for the toxic potential of ambient PM samples. In addition, significant correlations were observed between the oxidant generating potential and all toxicological endpoints. Study 2 revealed, that short-time inhalation of carbonaceous nanoparticles (150 µg/cm³) leads neither to pulmonary inflammation nor to an induction of oxidative DNA damage and associated induction of DNA repair genes in whole lung tissue of mouse or alveolar epithelial cells isolated from rats. Study 3 was performed to reveal the role of reactive oxygen species (ROS) from the phagocyte NADPH-oxidase during particle-elicited inflammation. Although an influx of inflammatory cells into the lung of wildtype as well as p47phox-/- mice was observed after pharyngeal aspiration of quartz particles, oxidative stress appeared only in wildtype mice. No effects were found regarding oxidative DNA damage and expression of DNA repair genes. In contrast, the importance of NADPH oxidase-mediated ROS formation in quartz induced genotoxicity was shown in a coculture model of bone-marrow derived neutrophils and A549 cells. The results of this thesis showed, that pulmonary inflammation is of major importance for the induction of oxidative DNA damage after particle exposure. NADPH-oxidase generated ROS by neutrophilic granulocytes seems to contribute to genotoxic effects after particle exposure. In addition to the pulmonary inflammation the chemical composition (transition metals, PAH, particle surface properties) of ambient particles seems to play an important role. | |||||||
| Lizenz: |  Urheberrechtsschutz | |||||||
| Fachbereich / Einrichtung: | Sonstige Einrichtungen/Externe » An-Institute » Institut für Umweltmedizinische Forschung (IUF) an der HHU | |||||||
| Dokument erstellt am: | 27.01.2010 | |||||||
| Dateien geändert am: | 27.01.2010 | |||||||
| Promotionsantrag am: | 08.12.2009 | |||||||
| Datum der Promotion: | 20.01.2010 |
