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    DNA repair and apoptosis: Roles in radiotherapy-related acute reactions in breast cancer patients
    (C M B Assoc, 2018) Batar, Bahadır; Mutlu, Tuba; Bostanci, Merve; Akın, Mustafa; Tuncdemir, Matem; Bese, Nuran; Güven, Mehmet
    Normal tissue reactions are therapy limiting factor for the effectiveness of the radiotherapy in cancer patients. DNA repair and apoptosis are estimated to be critical players of adverse effects in response to radiotherapy. Our aim was to define the association of DNA repair (ERCC1 and XPC) and apoptotic (BCL2, CASP3 and NFKB1) gene expression, DNA damage levels, apoptosis changes and DNA repair gene variations with the risk of acute side effects in breast cancer patients. The study included 100 women with newly diagnosed breast cancer; an experimental case group (n=50) with acute side effects and the control group (n=50) without side effects. Gene expression was analyzed by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). Micronucleus (MN) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) assays were performed to compare the DNA damage levels. Apoptosis was examined by TDT-mediated dUTP-biotin nick end-labeling (TUNEL) staining. ERCC1 rs3212986 and XPC rs3731055 polymorphisms were genotyped by real-time PCR technique. No significantly correlation of DNA repair and apoptosis gene expression and DNA damage levels with acute side effects in response to radiotherapy. Also, there was no association between apoptosis levels and acute effects. ERCC1 rs3212986 CC genotype showed a protective effect against radiotherapy-induced acute reactions (p<0.001; OR: 0.21; 95% CI=0.08-0.52). Our results suggest that apoptosis and DNA damage levels are not associated with acute radiosensitivity. DNA repair may affect the risk of acute reactions. Further studies are needed to validate the current findings.
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    The Long-Term Impact of Ionizing Radiation on DNA Damage in Patients Undergoing Multiple Cardiac Catheterizations
    (Humana Press Inc, 2023) Cimci, Murat; Batar, Bahadir; Bostanci, Merve; Durmaz, Eser; Karayel, Bahadir; Raimoglou, Damla; Guven, Mehmet
    Ionizing radiation (IR) exposures have increased exponentially in recent years due to the rise in diagnostic and therapeutic interventions. A number of small-scale studies investigated the long-term effect of IR on health workers or immediate effects of IR on patients undergoing catheterization procedures; however, the long-term impact of multiple cardiac catheterizations on DNA damage on a patient population is not known. In this study, the effects of IR on DNA damage, based on micronuclei (MN) frequency and 8-hydroxy-2 & PRIME;-deoxyguanosine (8-OHdG) as markers in peripheral lymphocytes, were evaluated in patients who previously underwent multiple cardiac catheterization procedures. Moreover, genetic polymorphisms in genes PARP1 Val762Ala, OGG1 Ser326Cys, and APE1 Asn148Glu as a measure of sensitivity to radiation exposure were also investigated in the same patient population. The patients who underwent & GE; 3 cardiac catheterization procedures revealed higher DNA injury in comparison to the patients who underwent & LE; 2 procedures, documented with the presence of higher level of MN frequency (6.4 & PLUSMN; 4.8 vs. 9.1 & PLUSMN; 4.3, p = 0.002) and elevated serum 8-OHdG levels (33.7 & PLUSMN; 3.8 ng/mL vs. 17.4 & PLUSMN; 1.9 ng/mL, p = 0.001). Besides, OGG1 Ser326Cys and APE1 Asn148Glu heterozygous and homozygous polymorphic types, which are related with DNA repair mechanisms, were significantly associated with MN frequency levels (p = 0.006 for heterozygous and p = 0.001 for homozygous with respect to OGG1 Ser326Cys, p = 0.007 for heterozygous and p = 0.001 for homozygous with respect to APE1 Asn148Glu). There was no significant difference in terms of PARP1 Val762Ala gene polymorphism between two groups.