Unit:
Faculty of MedicineLibrary of the School of Health Sciences
Dissertation committee:
Καραΐσκος Παντελής, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Γεωργακίλας Αλέξανδρος, Καθηγητής, Σχολή Εφαρμοσμένων Μαθηματικών και Φυσικών Επιστημών, ΕΜΠ
Παπαγιάννης Παναγιώτης, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Παντελής Ευάγγελος, Επίκουρος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Λυμπεροπούλου Γεωργία, Λέκτορας, Ιατρική Σχολή, ΕΚΠΑ
Τερζούδη Γεωργία, Ερευνήτρια Α΄, Εργαστήριο Υγειοφυσικής, Ραδιοβιολογίας & Κυτταρογενετικής, ΙΠΡΕΤΕΑ, ΕΚΕΦΕ «Δημόκριτος»
Παραβατού Μαρία, Ερευνήτρια Α’, Εργαστήριο Υγειοφυσικής, Ραδιοβιολογίας & Κυτταρογενετικής, ΙΠΡΕΤΕΑ, ΕΚΕΦΕ «Δημόκριτος»
Original Title:
Διερεύνηση της επίδρασης των χαμηλών δόσεων ιοντίζουσας ακτινοβολίας σε μοριακό (DNA) και κυτταρογενετικό (χρωμοσωματικό) επίπεδο κατά την έκθεση ασθενών σε αιμοδυναμικές πράξεις
Translated title:
Investigation of the effect of low doses of ionizing radiation on molecular (DNA) and cytogenetic (chromosomal) level during exposure of patients to cardiac interventional procedures
Summary:
The increase in the number of patients exposed to ionizing radiation in cardiovascular procedures, either diagnostic or therapeutic, is constantly increasing in the last decade. Τhere is a strong linear correlation between the exposure to ionizing radiation and cancer risk for doses ≥100mSv. The respective correlation concerning low loses, such as those very often delivered to patients and medical staff in interventional cardiology, remains ambiguous. The correlation between the exposure to low ionizing radiation doses and carcinogenesis could be underpinned by epidemiological studies, which however demand high statistic power and patients’follow-up for many years. Alternatively, this relationship could be assessed by studying the mechanism of radiation-induced carcinogenesis and its potential activation with radiobiological experiments and also by detecting and quantitating biological effects essential for risk estimation in interventional cardiology.
The aim of the present Ph.D. thesis, is the investigation of the effects of low ionizing radiation doses, at the molecular, chromosomal and cellular level, and the potential activation of carcinogenesis. The experimental design is focused on the radiation-induced DNA damage and repair through the phosphorylation of the H2AX histone to form γ-Η2AX foci and the formation of chromosomal aberrations, micronuclei and asymmetric cell divisions which may lead to «chromothripsis» and the random rearrangement of the genetic material. For this purpose, peripheral blood samples were collected from 30 adult patients, who underwent ordinary interventional cardiology procedures in the laboratory of Onassis Cardiac Surgery Centre.
Blood samples from independent donors were also irradiated in vitro with low doses of ionizing radiation at the laboratory of Health Physics, of the National Centre for Scientific Research «Demokritos». The mean values of all patients as a group for the dicentric analysis, the γ-H2AX foci and the micronucleus test showed statistically significant increased yields relative to baseline following medical exposure. However, it was observed that there was no significant increase in the number of chromosomal aberrations at the individual level, whereas only a 25% of the whole group studied showed a significant increase in the micronuclei at the individual level. The results of this study demonstrated that only the γ-H2AX biomarker enables detection of statistically significant differences at the individual level for almost all patients (91%). These observations point up the clear advantage of the use of γ-Η2AX foci over the conventional dicentric and micronuclei assays for low level doses. Furthermore, 24 hours after exposure, residual γ-H2AX foci were still detectable in irradiated lymphocytes. Their repair kinetics was found to vary significantly among the individuals, and their decline ranged from 25% to 95.6% of the maximum values obtained immediately after the exposure.
Moreover, the Life Attributable Risk from the interventional procedure based on the γ-H2AX foci induction was found considerably greater than the one estimated using the Linear Non Threshold Model assumption. The remarkable difference in the magnitude of this increase is explained, in part, by the use of 60Co for the in vitro irradiation in this work, since the risk from exposure to x-rays could be greater than that for γ rays.
Finally, the in vitro experiments perfomed in order to detect the existence of asymmetric cell divisions for several time intervals post-irradiation pointed that there is a significant increase in asymmetric cell division even after a low dose of 50 mGy. However, the hypothesis tested for radiation-induced carcinogenesis after low dose exposure, by detecting chromothripsis-like chromosomal aberrations, could not be supported by the results obtained.
Main subject category:
Health Sciences
Keywords:
Low doses, Ionizing radiation, Interventional cardiology, Chromosomal aberrations, γ-H2AX foci, Micronuclei, Phosphorylated histone, Chromothriphis, Asymmetric cell divisions, DNA repair
Number of references:
101
