KIT | KIT-Bibliothek | Impressum | Datenschutz

Comparison between micro- and nanosized copper oxide and water soluble copper chloride : Interrelationship between intracellular copper concentrations, oxidative stress and DNA damage response in human lung cells

Strauch, Bettina Maria 1,2; Niemand, Rebecca Katharina 1,2; Winkelbeiner, Nicola Lisa 1,2; Hartwig, Andrea 1,2
1 Institut für Angewandte Biowissenschaften (IAB), Karlsruher Institut für Technologie (KIT)
2 Institut für Toxikologie und Genetik (ITG), Karlsruher Institut für Technologie (KIT)


Background: Nano- and microscale copper oxide particles (CuO NP, CuO MP) are applied for manifold purposes, enhancing exposure and thus the potential risk of adverse health effects. Based on the pronounced in vitro cytotoxicity of CuO NP, systematic investigations on the mode of action are required. Therefore, the impact of CuO NP, CuO MP and CuCl₂ on the DNA damage response on transcriptional level was investigated by quantitative gene expression profiling via high-throughput RT-qPCR. Cytotoxicity, copper uptake and the impact on the oxidative stress response, cell cycle regulation and apoptosis were further analysed on the functional level.
Results: Cytotoxicity of CuO NP was more pronounced when compared to CuO MP and CuCl₂ in human bronchial epithelial BEAS-2B cells. Uptake studies revealed an intracellular copper overload in the soluble fractions of both cytoplasm and nucleus, reaching up to millimolar concentrations in case of CuO NP and considerably lower levels in case of CuO MP and CuCl₂. Moreover, CuCl₂ caused copper accumulation in the nucleus only at cytotoxic concentrations. Gene expression analysis in BEAS-2B and A549 cells revealed a strong induction of uptake-related metallothionein genes, oxidative stress-sensitive and pro-inflammatory genes, anti-oxidative defense-associated genes as well as those coding for the cell cycle inhibitor p21 and the pro-apoptotic Noxa and DR5. ... mehr

Volltext §
DOI: 10.5445/IR/1000073192
DOI: 10.1186/s12989-017-0209-1
Zitationen: 70
Web of Science
Zitationen: 66
Zitationen: 71
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Angewandte Biowissenschaften (IAB)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2017
Sprache Englisch
Identifikator ISSN: 1743-8977
KITopen-ID: 1000073192
Erschienen in Particle and fibre toxicology
Verlag Springer Fachmedien Wiesbaden
Band 14
Heft 1
Seiten Art. Nr. 28
Bemerkung zur Veröffentlichung Gefördert durch den KIT-Publikationsfonds
Schlagwörter Copper oxide nanoparticles, Oxidative stress, Gene expression profiling, High-throughput RT-qPCR, DNA damage response, Copper uptake and intracellular distribution
Nachgewiesen in Scopus
Web of Science
KIT – Die Forschungsuniversität in der Helmholtz-Gemeinschaft
KITopen Landing Page