Formation und Kinetik von DNA-Doppelstrangbrüchen nach Bestrahlung in Abhängigkeit von Kontrastmittelgabe und Bestrahlungstemperatur

Jeder Mensch ist in seinem Leben einer gewissen Strahlendosis ausgesetzt. Diagnostische Verfahren in der Medizin bilden mit einem Anteil von ungefähr 14 % den größten vom Menschen verursachten Anteil an ionisierender Strahlung weltweit. Ionisierende Strahlung kann über verschiedene Schäden an der D...

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Bibliographic Details
Main Author: Eble, Katharina
Contributors: Heverhagen, Johannes T. (Prof. Dr. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2011
Online Access:PDF Full Text
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Table of Contents: Every person is frequently exposed to ionizing radiation. Diagnostic x-ray procedures present the largest man-made source of ionizing radiation exposure to humans that contributes about 14 % of the total annual exposure. Ionizing radiation can cause leukemia and other kinds of cancer through various damages to the DNA. DNA double-strand breaks (DSBs) are among the most significant damages that can initiate carcinogenesis. In addition, many imaging applications require the use of iodinated contrast agents. Nephro- and cytotoxic effects of these contrast agents are already known. However, there are only few studies on whether the use of contrast agents has an additional influence on the formation and repair of DNA damage which is caused by the exposure to diagnostic x-rays. Although heat-induced γ-H2AX foci have been described recently, studies about the influence of temperature on the induction and repair of radiation-induced DSBs are rare and contradictory. Especially few research results exist about the combination of ionizing radiation and hypothermic temperatures. As part of this work for the quantification of DNA double-strand breaks I used the depiction of γ-H2AX foci via immunfluorescence. I performed the experiments at room temperature, 4 °C and 37 °C, each with and without contrast agent. To be able to make statements about the correlation of the radiation dose and the induction of DSBs, human lymphozytes were radiated in vitro with 20 mGy, 100 mGy, 200 mGy and 1000 mGy per experimental series. To measure the repair of the DSBs over the time, the lymphozytes were fixed immediately, 30 min, 1 h, 2 h and 24 h after radiation. The results of the study show a linear relationship between radiation dose and the formation of γ-H2AX foci. A decrease of foci within 24 h after radiation was found. Furthermore after 24 h I could still find an elevated level of foci. At the experiments with the application of iodinated contrast agent, I was able to prove that the formation of DSBs was increased if contrast agent was present during radiation. In addition, the results showed that the repair capacity in the experiments with contrast agent was not restricted. The further results showed that the formation of γ-H2AX foci was decelerated at low temperatures.