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In vitro Assessment of Arsenic Immune Toxicity using Human Cord Blood and Murine Bone Marrow Cells

In vitro Assessment of Arsenic Immune Toxicity using Human Cord Blood and Murine Bone Marrow Cells


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FERRARIO, Daniele, 2009. In vitro Assessment of Arsenic Immune Toxicity using Human Cord Blood and Murine Bone Marrow Cells [Dissertation]. Konstanz: University of Konstanz

@phdthesis{Ferrario2009vitro-7531, title={In vitro Assessment of Arsenic Immune Toxicity using Human Cord Blood and Murine Bone Marrow Cells}, year={2009}, author={Ferrario, Daniele}, address={Konstanz}, school={Universität Konstanz} }

<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#" xmlns:foaf="http://xmlns.com/foaf/0.1/" xmlns:void="http://rdfs.org/ns/void#" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/7531"> <dc:language>deu</dc:language> <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/7531"/> <dcterms:abstract xml:lang="eng">Inorganic arsenic and its metabolites are transplacentally active metalloids that have been observed to exert immunosuppressive effects both on humans and animals. Hematopoietic cells coming both from human cord blood or murine bone marrow offer an excellent tool for monitoring the immunotoxic effects of arsenic in vitro. In this study the effects of inorganic arsenic, its metabolites dimethylarsinic acid (DMAV), monomethylarsonic acid (MMAV) and monomethylarsonous acid (MMAIII), and the co-exposure with another contaminant (atrazine) have been assessed on the capacity of hematopoietic progenitors to give rise to granulocyte-macrophage colonies (CFU-GM). This evaluation was performed in both sexes, both on human cord blood cells and murine bone marrow cells. The results suggest an immunosuppressive role of arsenic at micro-molar concentration (1µM) on CFU-GM colonies in vitro, without any gender or inter-species differences in sensitivity to arsenic toxicity. On the contrary, at sub micro-molar concentration (0.0001µM) arsenic exerted a proliferative activity on CFU-GM colonies in vitro depending on the sex tested. Only female CFU-GM colonies were modulated. Both DMAV and MMAV did not exerted toxicity, whereas MMAIII was at least five times more toxic to the CFU-GM compared to arsenic. Some possible molecular mechanisms modulated by arsenic exposure were also investigated. It was shown that at sub micro-molar concentration, arsenic was able to increase the telomerase expression maintaining both telomere length, cell viability, possibly through the increasing expression of ras and myc oncogenes. Female donors were the more sensitive gender to the modulation of these molecular pathways, after low micro-molar arsenic exposure. At micro-molar concentration, we observed a decrease in the cell viability of human cord blood cells, together with a decreased telomere length, possibly due to increased reactive oxygen species production. In-utero and juvenile exposure of mice to arsenic at the concentration of 1mg/l did not cause modulations on the CFU-GM colonies proliferation in both genders. Nevertheless, a strong modulation in cancer-related gene expression of female donors has been observed. A dramatic increase in the GM proliferation was observed in female donors after co-exposure of arsenic with atrazine. An increase in the expression of estrogen receptor beta was observed for both genders, even if more significant for male donors. It can be concluded that arsenic exerts a double effect depending on the concentration on haematopoietic and immune progenitors. In addition, gender differences in the toxic outcome of arsenic do exist, especially for low arsenic exposures, even if the mechanisms related to these differences have not been fully understood.</dcterms:abstract> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-03-24T17:35:10Z</dcterms:available> <dc:contributor>Ferrario, Daniele</dc:contributor> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dc:creator>Ferrario, Daniele</dc:creator> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <dcterms:title>In vitro Assessment of Arsenic Immune Toxicity using Human Cord Blood and Murine Bone Marrow Cells</dcterms:title> <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/7531/1/Diss_Ferrario.pdf"/> <dcterms:rights rdf:resource="https://kops.uni-konstanz.de/page/termsofuse"/> <foaf:homepage rdf:resource="http://localhost:8080/jspui"/> <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/7531/1/Diss_Ferrario.pdf"/> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-03-24T17:35:10Z</dc:date> <dc:rights>terms-of-use</dc:rights> <dc:format>application/pdf</dc:format> <dcterms:issued>2009</dcterms:issued> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> </rdf:Description> </rdf:RDF>

Dateiabrufe seit 01.10.2014 (Informationen über die Zugriffsstatistik)

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