RNA microarray analysis for the detection of systemic effects following exposure to ionizing radiation

Postgraduate Thesis uoadl:1333103 697 Read counter

Unit:
Κατεύθυνση Βιοπληροφορική
Library of the School of Science
Deposit date:
2017-03-10
Year:
2017
Author:
Yeles Konstantinos
Supervisors info:
Αλέξανδρος Γεωργακίλας, Αναπληρωτής Καθηγητής, Τομέας Φυσικής,
Σχολή εφαρμοσμένων Μαθηματικών και Φυσικής, Εθνικό Μετσόβιο Πολυτεχνείο
Original Title:
Ανάλυση μικροσυστοιχιών RNA για την ανίχνευση συστημικών φαινομένων μετά από έκθεση σε ιοντίζουσα ακτινοβολία
Languages:
Greek
Translated title:
RNA microarray analysis for the detection of systemic effects following exposure to ionizing radiation
Summary:
Nowadays, the ever- increasing use of ionizing radiation in medical applications for the diagnosis and treatment of diseases has led to the study of new interaction phenomena effecting the living matter. Ionizing radiation carries sufficient energy to cause the release of electrons from atoms and molecules resulting in their ionization. Ionizing radiation effects are differentiated into direct, that results from the direct destruction of bonds and other damages due to the primary energy deposition of charged particles and photons that ionize atoms and indirect effects, that cause secondary production of electrons and other active molecules. Ionizing radiation is harmful and potentially lethal to living material in two different ways, either with a harmful effect on the tissues to high doses of either through mutations in somatic cells and cancer formation. Besides the targeted effect on the irradiated cells, it has been found that it causes non-targeted effects in nearby healthy cells, which are called radiation induced bystander effects. The study of these phenomena has been going on for two decades revealing a variety of biological characteristics. Two major signaling pathways have been shown to be involved in the above-mentioned phenomena and the communication occurs either by gap junctions or by factors secreted for intercellular communication. Various studies have shown that damage has been found in bystander cells similar to those irradiated such as genomic instability, micronuclei formation, changes in the expression of miRNA, damage in the DNA and apoptosis. A breakthrough discovery states that the above-mentioned phenomena do not affect different type of cells in the same way and that there is a different response depending on the subcategory of ionizing radiation used. The aim of this thesis is to establish the nature of these radiation induced bystander effects by developing statistical microarray data analysis techniques and their use in bioinformatics functional analysis tools that lead to the identification of the molecular pathways and their functions in these phenomena. For the analysis 7 different data sets from the database repository of high throughput gene expression data Gene Expression Omnibus (GEO) were used, 4 of which revealed statistically significant results. Programming language R and Bioconductor bioinformatics packages were used. For the functional analysis BioInfoMiner and EnrichR, which are online bioinformatics tools, were also used. The results revealed already known mechanisms in the literature and different responses to different classes of ionizing radiation. Particularly regarding α-particles and carbon-ions ionizing radiation distinct response mechanisms were observed in bystander cells. In the data sets that 0.5 Gy alpha particle ionizing radiation was used, at 0,5 and 4 hours RNA extraction after the irradiation, we noticed a great response to oxidative stress and inflammation through metallothioneins, cytokines, chemokines (MT1X, CXCL2, IL1B, PTGS2), response to protein damage and heat (HSPH1, DNAJA1), induction of the wound repair mechanisms and negative regulation of replication. In the data sets that 0,12 Gy and 0,013 Gy carbon ion ionizing radiation was used at 2 and 6 hours RNA extraction after the irradiation, we noticed a response to inflammation (PTGS2, IL1A, IL1B) and many apoptotic pathways. We also noticed a large difference in radiation induced bystander effects according to the different type of cell. In normal bystander cells a response was observed. In cancer and immortalized cells there was no statistically significant differentiation in the expression of genes. These results revealed several mechanisms involved in basic response of bystander cells to the proximity effects that can be used to study and verify more specific bystander cell responses.
Main subject category:
Science
Keywords:
BIOINFORMATICS, IONIZING RADIATION, MICROARRAYS, BYSTANDER CELLS, BYSTANDER EFFECT, RADIATION, RADIATION-INDUCED BYSTANDER EFFECTS, INFLAMMATORY RESPONSE
Index:
Yes
Number of index pages:
4
Contains images:
Yes
Number of references:
191
Number of pages:
173
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