000811468 001__ 811468
000811468 005__ 20210601120432.0
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000811468 020__ $$a978-3-89336-502-9
000811468 037__ $$aFZJ-2016-03939
000811468 041__ $$aGerman
000811468 1001_ $$0P:(DE-HGF)0$$aTurtoi, Andrei$$b0$$eCorresponding author$$gmale$$ufzj
000811468 245__ $$aUntersuchung frühzeitiger Reaktionen lymphozytärer Proteine auf Gamma-Bestrahlung humanen Vollbluts und deren Dosisabhängigkeit: Voraussetzung für die Entwicklung eines individuellen strahlenbiologischen Dosimeters
000811468 260__ $$aJülich$$bForschungszentrum Jülich GmbH Zentralbibliothek, Verlag$$c2007
000811468 300__ $$a97 S.
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000811468 4900_ $$aSchriften des Forschungszentrums Jülich. Reihe Lebenswissenschaften / Life Sciences$$v40
000811468 520__ $$aThe present thesis is concerned with the issues involved in obtaining reliable experimental data permitting a retrospective assessment of radiation-induced doses at the time of application or contamination. In order to provide prompt medical treatment of those injured in accidents with ionizing radiation, biological procedures that can be implemented swiftly and at an early stage are required both to determine the radiation dose originally received as well as to assess the course of the dosedependent biological reactions on the basis of individual sensitivity to radiation. To this end, in the present thesis the lymphocyte proteins (phosphoproteins and total proteins) in blood taken from test subjects who had been exposed to $\gamma$-radiation (applied dose: 0-4 Gy) were analysed just 15 minutes after completing irradiation by means of 2D gel electrophoresis. Only those early-response proteins (ERPROs) that displayed a significant radiation-induced change were identified by nano-HPLC-MS/MS. For validation purposes, the dose-dependent gene expression of some of these proteins was determined by RT-qPCR. The following ERPROs displayed pronounced early reactions in the form of changes of concentration in comparison to unirradiated control samples: talin-1, talin-2, $\beta$-actin, mutant $\beta$-actin, peroxin-1 and also the phosphoproteins annexin-A6, MHC-binding protein-2, zyxin-2, interleukin-17E and phosphoglycerate kinase-1. The majority of the lymphocyte ERPROs represent proteins responsible for changes to the cytoskeleton, proliferation and cell cycle, modulation of immunoreactions as well as protein degradation and energy production. Other cellular processes may not have been determined due to the sensitivity restrictions of the 2D-PAGE and MS methods, but cannot be excluded. Gene expression studies revealed that a combination of methods, comprising RT-qPCR and 2D-PAGE as well as DNA microarray and Western blot, may in future be able to overcome these restrictions. The slopes of the curves from concentration measurements of various early response proteins after doses had been applied in the 0 and 4 Gy range yielded a characteristic arrangement or pattern representative of an individual. In case of contamination, this pattern prepared ex vivo serves as a reference for identifying the originally unknown dose, thus creating the necessary condition for applying an individual radiation biodosimeter . This thus provides for the first time an experimental means of biologically quantifying in retrospect radioactive doses in the 0 and 4 Gy range after a relatively short time.
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