Entstehung und Reparatur von DNA-Doppelstrangbrüchen bei computertomographischen Untersuchungen in Bezug zum Patientenalter

Der demographische Wandel mit der Zunahme der Lebenserwartung in Deutschland und anderen Industriestaaten ist zu einem großen Teil durch medizinischen Fortschritt bedingt. Die jährliche Strahlendosis, der ein Mensch in Deutschland ausgesetzt ist, wird durch natürliche und zivilisatorische Strahlung...

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Bibliographic Details
Main Author: Schmitz-Beuting, Daniel
Contributors: Heverhagen, Johannes T. (Prof. Dr. med. Dr. rer. physiol.) (Thesis advisor)
Format: Dissertation
Language:German
Published: Philipps-Universität Marburg 2019
Medizin
Subjects:
y
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Table of Contents: The demographic change due to the raised expectation of life in Germany and other industrial states is to a high degree a result of medical progress. The annual radiation level that a human in Germany is exposed to is induced by natural and civilisation radiation. The greatest part of the average annual radiation level is caused by medical use of civilisation radiation. Diagnostic computed tomography examinations represent the biggest source of ionizing radiation. People of an advanced age have the highest amount of CT Scans taken. The worst consequence that can occur to human tissue under the influence of ionizing radiation is a double-strand break of the DNA. If a double-strand break is not detected or not sufficiently repaired, or through a controlled cell death induced as apoptosis destroyed, this break can lead to a mutation of the genetic information and possibly to malignant degeneration with the genesis of cancer. For the detection of DNA double-strand breaks in vivo in the low dose radiation range of mGy, as by CT examinations, the y-H2AX-Method is the golden standard. A DNA double-strand break after the influence of ionizing radiation causes the phosphorylisation of the under group H2AX of a histone protein of the DNA-molecule. The originated phosphorylated histone y-H2AX can be marked through a specific antibody, and through a second fluorescent antibody be visualised and determined under the fluorescence microscope. In former studies it was shown that one detected focus in the fluorescent microscope corresponds exactly with one DNA double-strand break, and that the reduction of foci corresponds with the repair of DNA double-strand breaks. In the first part of the present dissertation the genesis and the development of DNA double-strand breaks over 24 hours, as y-H2AX-Foci after a CT Examination in vivo, was investigated. In the second part the influence of age to the genesis and repair of DNA double-strand breaks was investigated. It took place with 47 patients who were subjected to a CT examination for medical reasons. Blood samples were taken before the CT examination and 5 minutes, 1 hour, 2 hours and 24 hours after the CT examination. The lymphocytes were isolated from the blood samples, and with the y-H2AXMethod the DNA double-strand breaks identified. In every patient it showed an explicit increase of DNA double-strand breaks 5 minutes after the CT examination. It confirmed that DNA double-strand breaks in vivo in low dose radiation range can be detected successfully through the y-H2AX method. The number of foci correlate with the range of earlier studies. The study shows in progression a continues decrease of foci in every patient as evidence of repair of the DNA double-strand breaks. To study the potential influence of age to the genesis and reparation of DNA double-strand breaks the patients were grouped in 7 age groups, aged from 20 to 89 years. Before the CT examination an outstandingly increased number of DNA double-strand breaks were found in the groups with the oldest patients, aged from 70 to 79 years and from 80 to 89 years. 5 minutes after the CT examination the patients aged from 40 to 49 years showed the most DNA double-strand breaks. 24 hours after the CT examination the most DNA double-strand breaks were proven in the youngest age group from 20 to 29 years.