title: Cellular uptake of platinum nanoparticles in human colon carcinoma cells and their impact on cellular redox systems and DNA integrity.
abstract: Supercritical fluid reactive deposition was used for the deposition of highly dispersed platinum nanoparticles with controllable metal content and particle size distribution on beta-cyclodextrin. The average particle size and size distribution were steered by the precursor reduction conditions, resulting in particle preparations <20, <100, and >100 nm as characterized by transmission electron microscopy and scanning electron microscopy (SEM). These particle preparations of different size distributions were used to address the question as to whether metallic platinum particles are able to invade cells of the gastrointestinal tract as exemplified for the human colon carcinoma cell line HT29 and thus affect the cellular redox status and DNA integrity. Combined focused ion beam and SEM demonstrated that platinum nanoparticles were taken up into HT29 cells in their particulate form. The chemical composition of the particles within the cells was confirmed by energy-dispersive X-ray spectroscopy. The potential influence of platinum nanoparticles on cellular redoxsystems was determined in the DCF assay, on the translocation of Nrf-2 and by monitoring the intracellular glutathione (GSH) levels. The impact on DNA integrity was investigated by single cell gel electrophoresis (comet assay) including the formation of sites sensitive to formamidopyrimidine-DNA-glycosylase. Platinum nanoparticles were found to decrease the cellular GSH level and to impair DNA integrity with a maximal effect at 1 ng/cm(2). These effects were correlated with the particle size in an inverse manner and were enhanced with increasing incubation time but appeared not to be based on the formation of reactive oxygen species.
authors.affiliation: Institut für Angewandte Biowissenschaften, Abteilung für Lebensmitteltoxikologie, Universitt Karlsruhe (TH), Karlsruhe, Germany.
authors.forename: Joanna
authors.initials: J
authors.lastname: Pelka
authors.forename: Helge
authors.initials: H
authors.lastname: Gehrke
authors.forename: Melanie
authors.initials: M
authors.lastname: Esselen
authors.forename: Michael
authors.initials: M
authors.lastname: Türk
authors.forename: Marlene
authors.initials: M
authors.lastname: Crone
authors.forename: Stefan
authors.initials: S
authors.lastname: Bräse
authors.forename: Thierry
authors.initials: T
authors.lastname: Muller
authors.forename: Holger
authors.initials: H
authors.lastname: Blank
authors.forename: Winfried
authors.initials: W
authors.lastname: Send
authors.forename: Volker
authors.initials: V
authors.lastname: Zibat
authors.forename: Patrice
authors.initials: P
authors.lastname: Brenner
authors.forename: Reinhard
authors.initials: R
authors.lastname: Schneider
authors.forename: Dagmar
authors.initials: D
authors.lastname: Gerthsen
authors.forename: Doris
authors.initials: D
authors.lastname: Marko
mesh_terms: D002277:Carcinoma; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms; D020552:Comet Assay; D004249:DNA Damage; D043382:DNA-Formamidopyrimidine Glycosylase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D010984:Platinum / Q000737:chemistry* / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D010984:Platinum; D043382:DNA-Formamidopyrimidine Glycosylase; D005978:Glutathione