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Influence of High- and Low-LET Radiation on the Cardiac Differentiation of Mouse Embryonic Stem Cells

Helm, Alexander :
Influence of High- and Low-LET Radiation on the Cardiac Differentiation of Mouse Embryonic Stem Cells.
[Online-Edition: http://tuprints.ulb.tu-darmstadt.de/3619]
TU Darmstadt
[Ph.D. Thesis], (2013)

Official URL: http://tuprints.ulb.tu-darmstadt.de/3619

Abstract

The in utero exposure to ionising radiation poses a risk for the radiosensitive developing embryo. Effects of low-LET radiation on different developmental stages of the embryo are relatively well known due to experimental studies and epidemiological data. Data for effects on the very early stage of the embryonic development, particularly the effects of high-LET radiation instead are rather limited. However, unanticipated exposures of the early embryo to ionising radiation may occur through diagnostic or therapeutic applications or through radiation accidents. Additionally, protons and carbon ions are increasingly used in radiotherapy. Thus, a risk estimation of high-LET exposure especially to the early embryo is of a certain importance. To address this topic, pluripotent mouse embryonic stem cells resembling the blastocyst stage were irradiated with high-LET carbon ions or low-LET x-rays and subsequently differentiated to mimic the early embryonic development. The occurrence of spontaneously contracting cardiomyocytes was used as a marker to asses the radiation effects on the differentiation. Among others, cell inactivation, cell death and gene expression were analysed. A delay in the cardiac differentiation after radiation exposure was found. The results point to radiation-induced cell killing as the main effector of the developmental delay. Carbon ions were found to be more effective than x-rays.

Item Type: Ph.D. Thesis
Erschienen: 2013
Creators: Helm, Alexander
Title: Influence of High- and Low-LET Radiation on the Cardiac Differentiation of Mouse Embryonic Stem Cells
Language: English
Abstract:

The in utero exposure to ionising radiation poses a risk for the radiosensitive developing embryo. Effects of low-LET radiation on different developmental stages of the embryo are relatively well known due to experimental studies and epidemiological data. Data for effects on the very early stage of the embryonic development, particularly the effects of high-LET radiation instead are rather limited. However, unanticipated exposures of the early embryo to ionising radiation may occur through diagnostic or therapeutic applications or through radiation accidents. Additionally, protons and carbon ions are increasingly used in radiotherapy. Thus, a risk estimation of high-LET exposure especially to the early embryo is of a certain importance. To address this topic, pluripotent mouse embryonic stem cells resembling the blastocyst stage were irradiated with high-LET carbon ions or low-LET x-rays and subsequently differentiated to mimic the early embryonic development. The occurrence of spontaneously contracting cardiomyocytes was used as a marker to asses the radiation effects on the differentiation. Among others, cell inactivation, cell death and gene expression were analysed. A delay in the cardiac differentiation after radiation exposure was found. The results point to radiation-induced cell killing as the main effector of the developmental delay. Carbon ions were found to be more effective than x-rays.

Divisions: 10 Department of Biology > Radiation Biology and DNA Repair
10 Department of Biology
Date Deposited: 20 Oct 2013 19:55
Official URL: http://tuprints.ulb.tu-darmstadt.de/3619
URN: urn:nbn:de:tuda-tuprints-36194
Referees: Durante, Prof. Dr. Marco and Layer, Prof. Dr. Paul G.
Refereed / Verteidigung / mdl. Prüfung: 19 July 2013
Alternative Abstract:
Alternative abstract Language
Eine Strahlenexposition in utero stellt ein Risiko für den sich entwickelnden Embryo dar. Die Effekte von Niedrig-LET Strahlung auf verschiedene Embryonalstadien sind aufgrund von in vivo-Studien und epidemiologischen Daten weitestgehend bekannt. Daten für Effekte auf das früheste Stadium, die Präimplantationsphase, und speziell für Effekte von Hoch-LET Strahlung sind dagegen kaum verfügbar. Eine unbeabsichtigte Bestrahlung des frühen Embryos kann jedoch bei diagnostischen oder therapeutischen Anwendungen von ionisierender Strahlung oder bei Strahlenunfällen auftreten. Des Weiteren werden Protonen und Kohlenstoffionen vermehrt in der Strahlentherapie eingesetzt. Eine bessere Risikoabschätzung zur Wirkung von Hoch-LET Strahlung besonders auf den sehr frühen Embryo ist daher von Interesse. Um hierzu beizutragen, wurden in der vorliegenden Arbeit pluripotente embryonale Mausstammzellen verwendet, die mit dem frühen Embryonalstadium der Blastozyste vergleichbar sind. Im Anschluss an die Bestrahlung der Stammzellen mit Kohlenstoffionen (Hoch-LET Strahlen) und Röntgenstrahlen (Niedrig-LET Strahlen) wurden diese als Modell für die frühe Embryonalentwicklung differenziert. Das Auftreten von spontan kontrahierenden Kardiomyozyten wurde als Marker verwendet, um den Einfluss ionisierender Strahlung auf die Differenzierung zu erfassen. Neben weiteren Endpunkten wurden Zellinaktivierung, Zelltod und Genexpression untersucht. Die Experimente zeigten eine Verzögerung der kardialen Differenzierung nach Bestrahlung. Die Resultate weisen auf einen strahleninduzierten Zelltod als Hauptursache für die verzögerte Entwicklung hin. Kohlenstoffionen sind in diesem Zusammenhang effektiver als Röntgenstrahlen.German
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