Unit:
Faculty of MedicineLibrary of the School of Health Sciences
Dissertation committee:
Τραφαλής Δημήτριος Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Μουρούζης Ιορδάνης Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Πάντος Κωνσταντίνος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Γκρινάτσος Ιωάννης Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Σιάσος Γεράσιμος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Κοντός Μιχαήλ Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Βρυώνη Γεωργία Αναπληρωτής Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Ανίχνευση βλαβών DNA σε σωματικά υγρά σε ασθενείς με καρκίνο μαστού που υποβάλλονται σε ακτινοθεραπεία. Συσχέτιση με το βαθμό της δερματικής τοξικότητας
Translated title:
Detection of DNA damage in body fluids in breast cancer patients undergoing radiotherapy. Correlation with skin toxicity grade
Summary:
Breast cancer belongs to the most common malignancies worldwide. Radiation therapy plays an adjuvant role in anticancer treatment. During cell exposure to radiation, the produced reactive oxygen (ROS) and nitrogen species (RNS) induce the formation of 8-hydroxy-2- deoxyguanosine (8-OHdG) and 8-nitroguanine (8-NG), respectively. Taking into consideration that ionizing radiation is administered during radiotherapy, the scientific interest of the present study focuses on the detection of 8-OHdG and 8-NG in irradiated breast cancer patients and the investigation of the above DNA lesions as predictive markers of radiation dermatitis, one of most common side-effects induced by radiation therapy.This research hypothesis was explored according to the ELISA method which was conducted in order to test the blood serum samples collected from 33 patients who had underwent postoperative radiotherapy. The laboratory analysis was concentrated on the detection of DNA damage products, 8-OHdG and 8-NG, as well as glutathione (GSH) which is known for its antioxidant activity.Among all the tested clinical parameters, alterations in [8-OHdG] and [8-NG] levels are significantly associated with radiation dermatitis. Normalizing the altered [8-OHdG] and [8-NG] with BMI and BSA parameters, considerable correlations with radiation-induced dermal toxicity were revealed. Furthermore, the ratios [8-NG]/BMI and [8-NG]/BSA are strongly correlated with radiation dermatitis before the initiation of radiotherapy(P<0.05). Overall alterations in [8-OHdG] and [8-NG] levels are statistically correlated with the dermal toxicity during the time intervals D0-D14, D0-D28 and D0-D56 (P<0.005 and P<0.01, respectively). By contrast, relative alterations in [8-OHdG] levels are remarkably associated with dermal toxicity only during the time interval D0-D14 (P<0.05) while relative alterations in [8-NG] levels are correlated with radiation dermatitis during D0-D14 (P<0.05) and D14- D28 (P<0.05). The ability to predict the radiation-induced dermatitis based on 8-OHdG and 8- NG arises from the significant linear correlation between % relative alterations in [8-OHdG] and [8-NG] levels with dermatitis grade (P<0.001). As positive can be considered the correlations between % [GSH] overall reductions and dermatitis grade in the administered radiation doses of 2000 cGy (P<0.05) and 6000 cGy (P<0.005).To conclude, 8-OHdG and 8-NG may be suggested as predictive markers of radiation dermatitis in patients who undergo radiation therapy. Finally, with regard to GSH, the increased reduction of % [GSH] levels indicates a greater probability of developing dermal toxicity upon radiation treatment.
Main subject category:
Health Sciences
Keywords:
radiation therapy, 8-hydroxy-2’-guanosine, 8-nitroguanine, breast cancer, radiation dose, exposure time, dose-response relationships
Number of references:
354
