Description: Das Projekt "Cellular effects of Carbon Nanotubes" wird/wurde ausgeführt durch: ZMF - Center for Medical Research.Materials in the nanometer range (nanomaterials, NMs) dramatically change their physico-chemical properties and in general act more toxic than the respective bulk materials. As human exposure to NMs in the future is expected to increase also in medical applications, the toxic mechanism of such NMs has to be studied in more detail. Carbon nanotubes (CNTs) possess features that make them excellent candidates for medical imaging and treatment. CNTs developed for these applications are shorter and more hydrophilic to avoid the adverse effects caused by the CNTs used in technical applications. Epithelial cells and also phagocytes are important cellular targets because they are present at all physiological barriers. Acute exposure may cause cytotoxic and genotoxic effects. As CNTs are not biodegradable also chronic effects and effects of cellular accumulation have to be taken into account. Chronic exposure may impair phagocyte function; induce chronic inflammation and cause lysosomal dysfunction. With the trend towards an extended life expectancy in the population chronic toxic effects become increasingly important. These effects have only rarely been investigated thus far. This project aims to systematically investigate the role of two important parameters in the toxic action of CNTs, functionalization with carboxyl groups and size, with respect to acute and chronic effects in phagocytic and non phagocytic cells. Carboxyl-functionalized and plain single walled CNTs and multi walled CNTs of different sizes in addition to carboxyl-functionalized and plain polystyrene beads as controls will be studied. After physicochemical characterization in physiological fluids, the cytotoxic action is assessed by viability assays and by monitoring of cellular interaction. Necrosis, apoptosis, proliferation and generation of radicals are studied. Similar data are collected after prolonged exposure. In order to highlight pathways important in chronic exposure, dys-regulated pathways are identified by whole genome transcriptome analysis. The effect of accumulation is evaluated by determination of the amount of lysosomes and lysosomal activity according to dye uptake and proteolytic activity of cathepsins B and L. Genotoxicity is assessed by micronucleus formation, detection of the double-strand break marker y-H2AX and hypoxanthine-guanine phosphoribosyltransferase forward mutation assay. Action on macrophage function is analyzed according to phagocytosis, chemotaxis, and production of cytokines, nitric oxide and superoxide. These investigations identify the role of carboxyl functionalization and of the relation of diameter to length in the cellular effects for CNTs upon short- and long-term exposure. These data help to develop less toxic and more biocompatible CNTs.
SupportProgram
Origin: /Bund/UBA/UFORDAT
Tags: Genom ? Mutation ? Polystyrol ? Kohlenstoff-Nanoröhren ? Farbstoff ? Stickstoffmonoxid ? Material ? Biologische Abbaubarkeit ? Genotoxizität ? Makrophagen ? Stickoxide ? Zytotoxizität ? Gelöster organischer Kohlenstoff ? Langzeitbelastung ? Chemikalien ? Daten ? Exposition ? Monitoring ? Toxizität ? Medizintechnik ? Nanomaterialien ? Vermehrung ? Verwertung ? Wechselwirkung ?
License: cc-by-nc-nd/4.0
Language: Englisch/English
Time ranges: 2010-05-01 - 2013-05-31
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