Quantifizierung der Steigerung der DNA-Doppelstrangbrüche in der Computertomographie durch die i.v.-Gabe von jodhaltigem-Kontrastmittel- Einfluss verschiedener Störfaktoren

Da röntgenbasierte Untersuchungen über die letzten Jahre und Jahrzehnte im klinischen Alltag weltweit erheblich an Bedeutung gewonnen haben, ist es von immenser Wichtigkeit die Neben- und Auswirkungen zu kennen und richtig einordnen zu können. Neben anderen Kontrastmittelnebenwirkungen wie zum Beisp...

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Bibliographic Details
Main Author: Peters, Alan
Contributors: Heverhagen, J.T. (Prof. Dr. Dr.) (Thesis advisor)
Format: Dissertation
Published: Philipps-Universität Marburg 2015
Klinik für Strahlentherapie
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Table of Contents: The number and significance of examinations based on X-rays has become overwhelming in clinical day work. It is therefore of major importance to first of all know all possible side effects and secondly to evaluate them carefully and correctly. Besides well-known effects such as e.g. allergic reactions to the contrast agent, the DNA damages induced by X-rays are of major significance. In the past some investigations had shown a harmful effect of contrast agent-enhanced CT- examinations on the DNA. The aim of our study was to critically control those results with a larger sample of patients. We also had in mind that the main dose length product in CT-examinations was heavily decreased over the last few years which made an update necessary. Furthermore we wanted to examine the impact of certain disturbance variables on the result of the study. We chose to examine the impact of age, BMI and smoker-status on the DNA impairment, because those variables are easily achieveable in clinical day work and had shown an impact on DNA in other investigations. We used the by many trials well established method of immunofluorescent microscopy of the γH2AX-foci. These represent the ideal marker for DNA double strand breaks, the most severe damages of DNA. We collected lymphocytes from 225 patients, 53 undergoing a native examination (group 1), 172 receiving contrast agent (group 2), before and after their medically indicated CT-scan of the thorax. The samples were then immunostained and examined under the immunofluorescent microscop. The DNA-DSBs now could be detected as green foci and two experienced, independent and regarding to the time of sample achievement blinded examiners could analyze the samples. In a first step group 1 and group 2 were compared, secondly we took a closer look at the possible confounders age, BMI and smoker- statuts among the group 2. For this matter we divided the group into four big age groups (40-49 year-olds, 50-59 year-olds, 60-69 year-olds, 70-79 year-olds) and compared those. To examine the impact of BMI, we divided group 2 in three subgroups according to the BMI-classification in underweight (< 18.5 kg/m2), normalweight (18.5-24.9 kg/m2) and overweight (≥ 25.0 kg/m2) patients. To examine the impact of smoking we again divided group 2, this time comparing smokers to non-smokers, whereas all the patients which used to smoke in the past where assigned to the smokers group. Comparing group 1 to group 2 there was no statistically significant difference in rise of foci notable (p= 0.44). The mean foci achievement in group 2 was 0.0005 foci per cell, group 1 even showed 0.00015 less foci after the examination, both effects showing no statistical significance. Examining the impact of age on the foci numbers, we found significant less foci per cell among the youngest age group before the CT-scan compared to the other age groups (p= 0.0092). After the CT-scan the number was still smaller, but not statistically significant anymore (p= 0.0511). In the BMI groups there was a statistical significant difference between the overweight patients and the other weight groups regarding to the foci per cell before (p= 0.0019) and after (p= 0.0002) the CT-scan. Smokers showed additional 0.00074 foci per cell after the CT-scan, whereas non- smokers had only 0.00039 more foci per cell in mean. This difference was not statistically significant (p= 0.719). One has to take into account the rather high mean deviations, which symbolize the great individual differences in foci numbers among the patients. There were big differences in the backgroundlevels of foci compared to older investigations, which may be explained by different definitions of a focus among the analyzers. Our results partly contradict earlier investigations, this may be due to the decreasing dose length product used in CT-examinations over the last few years. We could show an effect of age and BMI on the evolving number of foci. But you have to take into account that our analysis was restricted to one time point only. In future studies, one could add a few more timepoints to evaluate the developement of foci numbers to further investigate the impact of the disturbance variables. Furthermore one should find a sensible subdivision of the smoker-group to be able to point out the effects of smoking on the DNA using immunofluorescent microscopy.