The Long-Term Impact of Ionizing Radiation on DNA Damage in Patients Undergoing Multiple Cardiac Catheterizations.

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'-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 ≥ 3 cardiac catheterization procedures revealed higher DNA injury in comparison to the patients who underwent ≤ 2 procedures, documented with the presence of higher level of MN frequency (6.4 ± 4.8 vs. 9.1 ± 4.3, p = 0.002) and elevated serum 8-OHdG levels (33.7 ± 3.8 ng/mL vs. 17.4 ± 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.

DNA repair and apoptosis: Roles in radiotherapy-related acute reactions in breast cancer patients.

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.

Toll-Like Receptors 2 and 4 Polymorphisms in Age-Related Macular Degeneration.

PURPOSE: Age-related macular degeneration (AMD) is a complex disorder with multifactorial etiology, caused by a combination of genetic and environmental factors. Innate immunity appears to play a key role in the pathogenesis of AMD. The purpose of this study was to determine whether common variation in the human toll-like receptors (TLRs) 2 and 4 alters the risk of AMD. PATIENTS AND METHODS: A total of 183 patients with AMD and 200 disease-free control subjects were enrolled. The genotyping of polymorphisms TLR2 (TLR2-Arg753Gln: rs5743708) and TLR4 (TLR4-Asp299Gly: rs4986790; TLR4-Thr399Ile: rs4986791) were done using real-time PCR. RESULTS: TLR2 Arg753Gln genotype had approximately four times greater risk of AMD compared with TLR2 Arg753Arg genotype (OR = 3.88; 95% CI: 1.76-8.75, p = 0.001). TLR2 Arg753Gln genotype was significantly higher in the patients with dry-type AMD (16%) and wet-type AMD (18%) than in the control (5%) subjects (p = 0.005 and p = 0.0008, respectively). There were no significant differences in the distribution of TLR4-Asp299Gly and TLR4-Thr399Ile genotypes between AMD patients and controls (p > 0.05). CONCLUSION: Our results suggest that TLR2 polymorphism may contribute to the pathogenesis of AMD.

Role of glutathione S-transferase M1, T1 and P1 gene polymorphisms in childhood acute lymphoblastic leukemia susceptibility in a Turkish population.

The variations between different individuals in the xenobiotic metabolizing enzymes' activity were shown to modify susceptibility to childhood acute lymphoblastic leukemia (ALL). Polymorphisms associated with genes coding for the glutathione S-transferase (GST) enzyme were known to affect the metabolism of different carcinogens. The aim of this study was to evaluate the influence of the GSTM1 and GSTT1 deletion polymorphisms, and the GSTP1 Ile105Val single nucleotide polymorphism (SNP) on the susceptibility to childhood ALL. The study was conducted in 95 children with ALL and 190 healthy control subjects from the Turkish population. The data revealed no difference in the prevalence of the GSTM1 and GSTT1 null genotypes between the childhood ALL patients and the controls. No association was found between GSTP1 Ile105Val variants and the susceptibility to childhood ALL, separately or in combination. Our findings suggested that the status of heritable GST polymorphism might not influence the risk of developing childhood ALL. Studies with a larger sample size are needed to evaluate and confirm the validity of our results.