OGG1 Research Articles

Evaluation of 8-Oxoguanine DNA Glycosylase-1(OGG1) Serum Levels in Patients with Type2 Diabetes Mellitus

: Chronic hyperglycemia in type 2 diabetes mellitus leads to elevated oxidative stress. As a consequence, the accumulation of reactive oxygen species (ROS)may cause additional damage to various biological macromolecules, including DNA. The current study aims to evaluate the DNA damage in type2 diabetic patients from Wasit Province by estimating the levels of 8-OHdG using ELISA. All samples were collected from the local community of Wasit province, Iraq. Forty-five type 2 diabetes mellitus patients (22 males and 23 females) and 35 healthy controls (17 males and 18 females) were genotyped for 8-oxoguanine DNA glycosylase-1(OGG1). Determination of 8-oxoguanine DNA glycosylase-1(OGG1) in sera of patients with T2DM and controls was done by using an Enzyme-linked immunosorbent assay ELISA.The results reveal highly significant differences, the OGG1 levels in the diabetic patients were higher than that of controls (646.96±2.14), controls (326.01±16.66), P= 0.0001. The OGG1 levels were elevated significantly among males and female’s patients withT2DM compared to the control group, 627.02±66.31 versus 679.68±63.27), P= 0.01 (381.85±29.33 versus 355.44±31.45), P = 0.0006, respectively. No significant differences were observed when comparing OGG1 levels between male and female patients with type2 diabetes, as well as in the control group: 627.03±66.31 versus 679.68±63.27, P=0.5974;381.85±29.36 vs.355.44±31.45, P=0.5478 in patients and controls respectively.679.68267±63.27413 versus627.02830±66.29612 with a non-significant difference P=0.5974. In conclusion levels of serum OGG1 are associated with diabetes mellitus

Modulation of 8-Oxoguanine DNA Glycosylase 1 (OGG1) Alleviated Anemia Severity and Excessive Cytokines Release during Plasmodium berghei Malaria in Mice.

The interplay of OGG1, 8-Oxoguanine, and oxidative stress triggers the exaggerated release of cytokines during malaria, which worsens the outcome of the disease. We aimed to investigate the involvement of OGG1 in malaria and assess the effect of modulating its activity on the cytokine environment and anemia during P. berghei malaria in mice. Plasmodium berghei ANKA infection in ICR mice was used as a malaria model. OGG1 concentration and oxidative stress levels in P. berghei-infected mice and their control counterparts were assessed during malaria using enzyme-linked immunosorbent assay. OGG1 activity in malaria mice was modulated using treatment with TH5487 and O8-OGG1 inhibitors. The effects of modulating OGG1 activity using OGG1 inhibitors on cytokine release and anemia during P. berghei malaria infection were assessed by cytometric bead array and measurement of total normal red blood cell count respectively. The plasma OGG1 level was significantly upregulated and positively correlated with parasitemia during P. berghei malaria in mice. Modulation of OGG1 ameliorated malaria severity by improving the total normal RBC count in TH5487 and O8-treated mice. Modulation of OGG1 with TH5487 caused significant reductions in serum levels of TNF-α, IFN-γ, IL-6, and IL-10. Similarly, OGG1 modulation activity using an O8-OGG1 inhibitor caused a significant reduction in serum levels of TNF-α, IL-2, IL-6, and IL-10. The findings indicate the involvement of OGG1 in the P. berghei malaria infection. OGG1 inhibition by TH5487 and O8-OGG1 inhibitors suppressed excessive cytokine release, and this may represent a novel therapeutic strategy for ameliorating the severity of malaria infection.

7-Hydroxy-3-(4'-methoxyphenyl) coumarin (C12) attenuates bleomycin-induced acute lung injury and fibrosis through activation of SIRT3.

Silent mating-type information regulation 2 homology 3 (SIRT3) is a member of the sirtuins family expressed in mitochondria performs deacetylation of metabolic enzymes and promotes longevity. 7-hydroxy-3-(4'-methoxyphenyl) coumarin (C12) is a small molecule first ever known for its direct activation of SIRT3. SIRT3 performs its function by balancing the redox system by activating manganese superoxide dismutase (MnSOD) and 8-Oxoguanine glycosylase (OGG1). For the first time, we reported that activation of SIRT3 by C12 attenuated bleomycin (BLM)-)-induced acute lung injury and pulmonary fibrosis. C12 prevented the oxidative stress and injury caused by BLM in alveolar epithelial cells (BEAS-2B) in in vitro and inhibited the fibrosis in transforming growth factor-beta (TGF-β) induced fibrosis in fibroblasts (MRC-5). Additionally, activation of SIRT3 by C12 in vivo mice model alleviated BLM-induced inflammation, collagen accumulation, cellular infiltration, and restoration of alveolar architecture by inhibiting TGF-β, smooth muscle actin (α-SMA), collagen-1A, collagen-3A, and mesenchymal markers. The protective effect of C12 was through activation of MnSOD and OGG1 in both in vitro and in vivo models suggesting C12 can be a potent SIRT3 activator and helps to treat fibrotic-related diseases.

AuNPs-based lateral flow strip genotoxicity biosensor by sensitive quantification of 8-oxodGuo

Development of rapid and sensitive methods for screening of large number of chemical pollutants with potential genotoxicity is in urgent demands. In this work, we reported a chemical genotoxicity sensor based on the lateral flow strip (LFS) quantification of the 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo). The proposed sensing strategy introduced human 8-oxoguanine DNA glycosylase (hOGG 1) and human apyrimidinic endonuclease (APE 1) to convert 8-oxodGuo to strand break. Then, the DNA conjugated gold nanoparticles (AuNPs) complexes could not be captured on test line (T-line), showing visible red color fading. Additionally, the mean grey value of the optical density in the T-line zone was analyzed by using a mobile phone camera and Image J software to quantify 8-oxodGuo. Under the optimized experimental conditions, the LFS DNA biosensor could detect the lowest concentration of 8-oxodGuo down to 0.2 pmol. To demonstrate its universal applications, in vitro generation of 8-oxodGuo by Rose Bengal under irradiation and Fe2+-mediated Fenton reagent were successfully measured. The detection limit of oxidative DNA damage induced by Rose Bengal or Fenton reagent could be down to 0.01 μM or 1 nM Fe2+/4 nM H2O2, respectively. The 10-fold higher sensitivity for Fenton reagent was attributed to much more severe damage than Rose Bengal, producing both DNA strand break and nucleobases conversion. The results demonstrated that the LFS DNA biosensor could detect oxidative DNA damage for the first time, showing its potential application for assessment of the genotoxicity of abundant chemical pollutants.

Oxidative stress on the male reproductive organs of wild mice collected from an area contaminated by radioactive materials in Fukushima

The Fukushima Daiichi Nuclear Power Plant accident caused the release of large amounts of radioactive material into the environment. Radiation from radionuclides cause DNA lesions, mainly via oxidation, which adversely affect wild organisms by damaging their germ cells. Here, we investigated the effects of radiation on the reproductive organs of Japanese field mice (Apodemus speciosus) by estimating the dose rate of radiation exposure, the accumulation of DNA lesions, and the expression of DNA repair enzymes. In highly contaminated areas, mouse testes received a radiation dose rate > 0.1 mGy/d. According to the International Commission on Radiological Protection, there is a very low probability of effects in the reference rat species at this exposure level. The results of the current study do not definitively conclude that the expression of 8-oxoguanine DNA glycosylase 1 and superoxide dismutase in mouse testes increase with dose rate and lifetime dose. However, 8-hydroxy-2′-deoxyguanosine accumulation increases in a dose rate- and lifetime dose-dependent manner in mouse testes, but is not observed in the sperm of the cauda epididymis. These results suggest that, although DNA lesions occurred in male germ cells of Fukushima mice, most were successfully repaired by DNA repair enzymes at the observed gene expression level.

Mitochondria-Targeted DNA Repair Glycosylase hOGG1 Protects Against HFD-Induced Liver Oxidative Mitochondrial DNA Damage and Insulin Resistance in OGG1-Deficient Mice.

8-oxoguanine DNA glycosylase-1 (OGG1) is a DNA glycosylase mediating the first step in base excision repair which removes 7,8-dihydro-8-oxoguanine (8-oxoG) and repairs oxidized nuclear and mitochondrial DNA. Previous studies showed that OGG1 deficiency results in an increased susceptibility to high-fat diet (HFD)-induced obesity and metabolic dysfunction in mice, suggesting a crucial role of OGG1 in metabolism. However, the tissue-specific mechanisms of how OGG1 deficiency leads to insulin resistance is unknown. Thus, in the current study, we used a hyperinsulinemic-euglycemic clamp to evaluate in-depth glucose metabolism in male wild-type (WT) mice and Ogg1-/- (Ogg1-KO) mice fed an HFD. Ogg1-KO mice fed HFD were more obese, with significantly lower hepatic insulin action compared to WT/HFD mice. Targeting human OGG1 to mitochondria protected against HFD-induced obesity, insulin resistance, oxidative mitochondrial DNA damage in the liver and showed decreased expression of liver gluconeogenic genes in Ogg1-KO mice, suggesting a putative protective mechanism. Additionally, several subunits of oxidative phosphorylation protein levels were noticeably increased in Ogg1-KO/Tg compared to Ogg1-KO mice fed an HFD which was associated with improved insulin signaling. Our findings demonstrate the crucial role of mitochondrial hOGG1 in HFD-induced insulin resistance and propose several protective mechanisms which can further direct the development of therapeutic treatment.

Cryopreservation of yellowtail kingfish (Seriola lalandi) sperm: Effects on metabolic enzymes and sperm quality

This study aimed to determine the effects of cryopreservation on sperm functionality and assess post-thaw sperm quality in yellowtail kingfish (Seriola lalandi). Milt designated for cryopreservation was frozen in a solution containing Cortland® medium +1.3 M Me2SO + 0.2 M glucose +2 % BSA in a 1:3 ratio (milt:cryoprotectant). Fresh milt was used as the control. The samples were frozen in 0.5 mL straws using a programmable freezing system. After thawing, the samples were evaluated for motility using Computer-Assisted Sperm Analysis (CASA) with a phase-contrast optical microscope. Additionally, flow cytometry and a multimodal reader were employed to assess various sperm parameters, including plasma membrane integrity (SYBR-14/PI), mitochondrial membrane potential (∆ΨMMit: JC-1), DNA fragmentation (TUNEL), ATP content (CellTiter-Glo®), intracellular calcium levels (Fluo-4 AM), lipid peroxidation (LPO), intracellular superoxide (DHE/SYTOX) and glutathione (GSH/GSSG) production, activities of glutathione peroxidase (GPx), catalase (CAT) and 8-oxoguanine glycosylase (OGG1), and detection of 8-hydroxydeoxyguanosine (8-OHdG). In cryopreserved milt, significant differences in motility (64.14 ± 2.2 %), plasma membrane integrity (61.5 ± 2.7 %), mitochondrial membrane potential (55.4 ± 2.4 %), DNA fragmentation (6.7 ± 1.1 %), ATP content (7.5 ± 1.5 nmol/109 spermatozoa), and intracellular calcium levels (59.8 ± 2.5 nM/109 spermatozoa) were observed compared to fresh milt. Differences were also noted in LPO, O2−i, GPx, GSH/GSSG, CAT, 8-OHdG and OGG1 between the cryopreserved and control groups. Additionally, correlations between sperm quality parameters, oxidative stress markers, and enzyme activity in cryopreserved spermatozoa were determined. These results suggest that cryopreservation induces significant alterations derived from oxidative damage in the functionality of yellowtail kingfish spermatozoa, and thus further research is necessary to explore the need for using antioxidants in the cryopreservation process of sperm from this species.

Human 8-Oxoguanine Glycosylase OGG1 Cleaves Abasic Sites and Covalently Conjugates to 3'-DNA Termini via Cysteine and Histidine Addition.

8-Oxoguanine glycosylase 1 (OGG1) repairs the major oxidative DNA damage, 8-oxo-2'-deoxyguanosine. It has been reported that OGG1 incises the most frequently formed DNA lesion, apurinic/apyrimidinic (AP) site, and in the process a stable DNA-OGG1 cross-link is formed. However, the chemical structure of the adduct is not characterized. Here, we report that DNA-OGG1 cross-links result from cysteine and histidine addition to incised AP sites at 3'-DNA termini.

8-Oxoguanine DNA Glycosylase 1 Recruits Transcription Factor STAT1 to Promote the Inflammatory Responses in Sickle Cell Disease

8-Oxoguanine DNA Glycosylase 1 Recruits Transcription Factor STAT1 to Promote the Inflammatory Responses in Sickle Cell Disease

OGG1: An emerging multifunctional therapeutic target for the treatment of diseases caused by oxidative DNA damage.

Oxidative DNA damage-related diseases, such as incurable inflammation, malignant tumors, and age-related disorders, present significant challenges in modern medicine due to their complex molecular mechanisms and limitations in identifying effective treatment targets. Recently, 8-oxoguanine DNA glycosylase 1 (OGG1) has emerged as a promising multifunctional therapeutic target for the treatment of these challenging diseases. In this review, we systematically summarize the multiple functions and mechanisms of OGG1, including pro-inflammatory, tumorigenic, and aging regulatory mechanisms. We also highlight the potential of OGG1 inhibitors and activators as potent therapeutic agents for the aforementioned life-limiting diseases. We conclude that OGG1 serves as a multifunctional hub; the inhibition of OGG1 may provide a novel approach for preventing and treating inflammation and cancer, and the activation of OGG1 could be a strategy for preventing age-related disorders. Furthermore, we provide an extensive overview of successful applications of OGG1 regulation in treating inflammatory, cancerous, and aging-related diseases. Finally, we discuss the current challenges and future directions of OGG1 as an emerging multifunctional therapeutic marker for the aforementioned challenging diseases. The aim of this review is to provide a robust reference for scientific researchers and clinical drug developers in the development of novel clinical targeted drugs for life-limiting diseases, especially for incurable inflammation, malignant tumors, and age-related disorders.

The OGG1 Ser326Cys Polymorphism and Its Association With DNA Damage and DNA Repair In Papillary Thyroid Cancer

Aim: Hydrogen peroxide, locally produced during thyroid hormone synthesis, leads to oxidative stress in the thyroid gland. Defective repair of oxidative DNA lesions contributes to tumor development. This study aimed to understand the importance of DNA damage and repair on thyroid cancer development through the impact of the DNA repair gene OGG1 Ser326Cys polymorphism that has clinical significance in untreated patients with papillary thyroid cancer. Methods: The study was performed with 70 patients with papillary thyroid cancer and 73 volunteers as control. In lymphocytes, endogenous DNA damage, H2O2-induced DNA damage, and DNA damage after repair were determined by comet assay. The polymerase chain reaction-restriction fragment length polymorphism method was performed for OGG1 genotyping. Results: Endogenous DNA damage, H2O2-induced DNA damage, and DNA damage after repair were higher in patients with thyroid cancer than in the controls (P

8-Oxoguanine DNA Glycosylase1 conceals oxidized guanine in nucleoprotein-associated RNA of respiratory syncytial virus.

Respiratory syncytial virus (RSV), along with other prominent respiratory RNA viruses such as influenza and SARS-CoV-2, significantly contributes to the global incidence of respiratory tract infections. These pathogens induce the production of reactive oxygen species (ROS), which play a crucial role in the onset and progression of respiratory diseases. However, the mechanisms by which viral RNA manages ROS-induced base oxidation remain poorly understood. Here, we reveal that 8-oxo-7,8-dihydroguanine (8-oxoGua) is not merely an incidental byproduct of ROS activity but serves as a strategic adaptation of RSV RNA to maintain genetic fidelity by hijacking the 8-oxoguanine DNA glycosylase 1 (OGG1). Through RNA immunoprecipitation and next-generation sequencing, we discovered that OGG1 binding sites are predominantly found in the RSV antigenome, especially within guanine-rich sequences. Further investigation revealed that viral ribonucleoprotein complexes specifically exploit OGG1. Importantly, inhibiting OGG1's ability to recognize 8-oxoGua significantly decreases RSV progeny production. Our results underscore the viral replication machinery's adaptation to oxidative challenges, suggesting that inhibiting OGG1's reading function could be a novel strategy for antiviral intervention.

Salubrious effects of proanthocyanidins on behavioral phenotypes and DNA repair deficiency in the BTBR mouse model of autism

Autism is a neurodevelopmental disorder distinguished by impaired social interaction and repetitive behaviors. Global estimates indicate that autism affects approximately 1.6% of children, with the condition progressively becoming more prevalent over time. Despite noteworthy progress in autism research, the condition remains untreatable. This serves as a driving force for scientists to explore new approaches to disease management. Autism is linked to elevated levels of oxidative stress and disturbances in the DNA repair mechanism, which may potentially play a role in its comorbidities development. The current investigation aimed to evaluate the beneficial effect of the naturally occurring flavonoid proanthocyanidins on the behavioral characteristics and repair efficacy of autistic BTBR mice. Moreover, the mechanisms responsible for these effects were clarified. The present findings indicate that repeated administration of proanthocyanidins effectively reduces altered behavior in BTBR animals without altering motor function. Proanthocyanidins decreased oxidative DNA strand breaks and accelerated the rate of DNA repair in autistic animals, as evaluated by the modified comet test. In addition, proanthocyanidins reduced the elevated oxidative stress and recovered the disrupted DNA repair mechanism in the autistic animals by decreasing the expressions of Gadd45a and Parp1 levels and enhancing the expressions of Ogg1, P53, and Xrcc1 genes. This indicates that proanthocyanidins have significant potential as a new therapeutic strategy for alleviating autistic features.

The Human 8-oxoG DNA Glycosylase 1 (OGG1) Ser326Cys Polymorphism in Infertile Men.

8-hydroxy-2'-deoxyguanosine (8-OHdG) is a form of oxidative DNA damage caused by oxidative stress (OS), which is considered a major factor in male infertility. The cellular defense system against 8-OHdG involves base excision repair (BER) with the enzyme 8-Oxoguanine DNA glycosylase 1 (OGG1). However, studies on the single-nucleotide polymorphism (SNP) OGG1 Ser326Cys have demonstrated that the Cys326Cys genotype could be the cause of an increment in oxidative DNA damage. In this study, the OGG1 Ser326Cys polymorphism and its effect on DNA oxidation were evaluated in 118 infertile men. Polymorphic screening was performed using TaqMan allelic discrimination assays, and oxidative DNA damage was evaluated through the quantification of 8-OHdG and total antioxidant capacity (TAC); in addition, electrical bioimpedance spectroscopy (EBiS) measurements were used as a reference for different electrical properties associated with 8-OHdG concentrations. The detected Cys (G) allele frequency (0.4) was higher compared to the allele frequency reported in the "Allele Frequency Aggregator" (ALFA) and "Haplotype Map" (HapMap) projects for American populations (0.21-0.29), suggesting that the Cys (G) allele carrier could be a factor associated with American infertile populations. The values of 8-OHdG were twofold higher in carriers of the Cys326Cys (GG) genotype than the other genotypes and, in concordance, the TAC levels were threefold lower in Cys326Cys (GG) genotype carriers compared to the other genotypes. Moreover, the EBiS magnitude exhibited potential for the detection of different oxidative damage in DNA samples between genotypes. The Cys326Cys (GG) genotype is associated with oxidative DNA damage that could contribute to male infertility.

Polymorphism of 8-oxoguanine DNA glycosylase -1(OGG1)in Iraqi Patients with Type2 Diabetes Mellitus

Chronic hyperglycemia in type 2 diabetes mellitus leads to elevated oxidative stress. As a consequence , the accumulation of reactive oxygen species (ROS)may cause additional damage to various biological macromolecules, including DNA. Several studies have demonstrated that oxidative stress plays an important role in the pathogenesis of type2 diabetes mellitus. The aim of this study is to investigate the association of polymorphisms of 8- oxoguanine DNA glycosylase-1(OGG1) repair gene polymorphism to the susceptibility of type 2 DM in an Iraqi population with T2DM patients from Wasit Province. All samples were collected from the local community of Wasit province, Iraq. Forty five type 2 diabetes mellitus patients (22 males and 23 females) and 35 healthy controls (17 males and 18 females) were genotyped for 8-oxoguanine DNA glycosylase-1(OGG1) using PCR- RFLP technique. In both patients and control groups, the distribution frequencies of genotypes and alleles of 8-oxoguanine DNA glycosylase-1(OGG1) A/G was inconsistent with the Hardy-Weinberg equilibrium in T2DM patients(χ2=49.542,P=(0.00001); χ2=82.0185,P=(0.0001) respectively. The Cys/Cys(mt/mt) OGG1 genotype was significantly higher in patients than controls(mt/mt;33(37%)vs,0.00 in controls. The Ser/Cys (wt/mt) was 7(16%) and 6(17%) in patients and controls respectively and Ser/Ser genotypes wt/wt; decreased significantly in patients 5(11%) vs,29(83%) in controls. The wt and mt allele frequencies of OGG1were highly significant between the two groups P=0.00001. The wt allele was the major one in control group with a percent of (90.28) vs. (18.89) in patients group. Whereas the mt the frequent allele in patients with a percent of (81.11) vs. (18.89).This further analysis showed that the individuals carrying the homozygous Cys/Cys(mt/mt) genotype were more likely to have increased the risk of T2DM very significantly with OR= 190.02800 (CI95% 10.8329 to 3342.2603) ,P=0.0003. The genotypes Ser/Ser( wt/wt) and Ser/Cys(wt/mt) decrease the association with T2DM with OR=0.0259 (CI95% 0.0072 to 0.0930), and 0.8904 (CI95% 0.2701 to 2.9347 )respectively, P= 0.0001 and 0.08486 for each genotype respectively, These results suggest that mt allele may be considered as risk allele of T2DM whereas the wt allele is protective agent T2DM.Association analysis showed that the type2 diabetes mellitus risk of females with OGG1 gene Cys/Cys( mt/mt) genotype was highly significant 81.4000 fold higher than that in controls OR= 81.4000 (CI 95% 4.3089 to 1537.7322), P= 0.0033.Ser/Cys( wt/mt) genotype increase the probability of the disease with OR = 1.7647 (CI 95% 0.3745 to 8.3154), P = 0.4727.Similary,Ser/Ser(wt/wt) genotype decrease the association with T2DM with OR= 0.0091 (CI95% 0.0009 to 0.0959), P = 0.0001.Type2 diabetes mellitus patients particularly with Cys/Cys(mt/mt) genotype increases the association about more than 111 times in males patients than that in controls OR= 111.3636 ( CI95% 5.7135 to2170.6226), P = 0.0019 While, genotypes Ser/Cys(wt/mt) and Ser/Ser (wt/wt) reduce the likelihood of T2DM with OR= 0.2222 ( CI95% 0.0209 to 2.3585),P = 0.2120 and 0.0476( CI95% 0.0091 to 0.2484), P= 0.0003 respectively. the genetic model for OGG1 in comparison between T2DM patients and controls . The dominant model indicated that patients and controls of (wt/mt+mt/mt) genotype increased significantly the association with T2DM in patients: (5/7 and 33) comparing with control (29/6 and 0.00) with OR (38.666),P=0.0001.The recessive model revealed that patients carrier the genotype (wt/wt+wt/mt) declined significantly the association with the disease :(33/5 and 7) in patients versus (0.00/29 and 6) in controls,OR=0.0053,P=0.0003.The Over-dominant model showed that patients with the genotype (wt/wt+mt/mt) in creased non-significantly the association with the disease when compare patients (7/5 and 33) with controls(6/29 and 0.00) ,OR=1.123,P=0.848

Human 8-oxoguanine glycosylase OGG1 binds nucleosome at the dsDNA ends and the super-helical locations

The human glycosylase OGG1 extrudes and excises the oxidized DNA base 8-oxoguanine (8-oxoG) to initiate base excision repair and plays important roles in many pathological conditions such as cancer, inflammation, and neurodegenerative diseases. Previous structural studies have used a truncated protein and short linear DNA, so it has been unclear how full-length OGG1 operates on longer DNA or on nucleosomes. Here we report cryo-EM structures of human OGG1 bound to a 35-bp long DNA containing an 8-oxoG within an unmethylated Cp-8-oxoG dinucleotide as well as to a nucleosome with an 8-oxoG at super-helical location (SHL)-5. The 8-oxoG in the linear DNA is flipped out by OGG1, consistent with previous crystallographic findings with a 15-bp DNA. OGG1 preferentially binds near dsDNA ends at the nucleosomal entry/exit sites. Such preference may underlie the enzyme’s function in DNA double-strand break repair. Unexpectedly, we find that OGG1 bends the nucleosomal entry DNA, flips an undamaged guanine, and binds to internal nucleosomal DNA sites such as SHL-5 and SHL+6. We suggest that the DNA base search mechanism by OGG1 may be chromatin context-dependent and that OGG1 may partner with chromatin remodelers to excise 8-oxoG at the nucleosomal internal sites.

Studies on the role of moderate doses of ionizing radiation-induced cellular senescence in mouse lung tissue

Purpose To investigate the role of moderate doses of ionizing radiation-induced cellular senescence in mouse lung tissue and whole-body inflammation levels. Material and methods Forty-two C57BL/6J mice were randomly divided into the control group, the 1, 3, and 7 days after 2 Gy irradiation group, and the 1, 3, and 7 days after 4 Gy irradiation group, with six mice in each group. The histopathology, cellular senescence, oxidative-antioxidant, DNA damage repair, and inflammation-related indicators of irradiated mice were examined. Results Compared with the control group, the histopathological scores, the positive area of senescence-associated-β-galactosidase (SA-β-Gal) staining, and the mRNA levels of senescence-related genes in the lung tissues in all dose groups increased on 1, 3, and 7 days after irradiation. In peripheral blood, erythrocytes, leukocytes, platelets, hemoglobin, 8-hydroxydeoxyguanosine (8-OHdG), C-reactive protein, and other indicators showed a different trend in all dose groups. The levels of malondialdehyde(MDA), superoxide dismutase (SOD), glutathione (GSH), and 8-OHdG in the lung tissue showed different trends after 2 Gy and 4 Gy irradiation. The 8-Oxoguanine DNA glycosylase 1 (hOGG1) and O-6-methylguanine-DNA methyltransferase (MGMT) mRNA levels showed a trend of increasing and then decreasing. The levels of whole-body inflammation were significantly correlated with the levels of indicators related to cellular senescence and damage repair in the lung tissue of mice. Conclusions The moderate doses of ionizing radiation induce oxidative stress, and DNA damage and increase DNA repair gene expression in mouse lung tissue. The lung tissue cellular senescence correlates with the level of whole-body inflammation.

The BCL11A transcription factor stimulates the enzymatic activities of the OGG1 DNA glycosylase.

The BCL11A transcription factor has previously been shown to interact with and stimulate the enzymatic activities of the NTHL1 DNA glycosylase and Pol β polymerase. Here we show that BCL11A and a smaller peptide encompassing amino acids 160 to 520 can interact with the 8-oxoguanine DNA glycosylase, OGG1, increase the binding of OGG1 to DNA that contains an 8-oxoguanine base and stimulate the glycosylase activity of OGG1. Following BCL11A knockdown, we observed an increase in oxidized purines in the genome using comet assays, while immunoassays reveal an increase in 8-oxoG bases. Structure-function analysis indicates that the stimulation of OGG1 by BCL11A requires the zinc fingers 1, 2 and 3 as well as the proline-rich region between the first and second zing finger, but a glutamate-rich region downstream of zinc finger 3 is dispensable. Ectopic expression of a small peptide that contains the three zinc fingers can rescue the increase in 8-oxoguanine caused by BCL11A knockdown. These findings, together with previous results showing that BCL11A stimulates the enzymatic activities of NTHL1 and the Pol β polymerase, suggest that high expression of BCL11A is important to protect cancer cells against oxidative DNA damage.

Effect of aflatoxin B1 and sterigmatocystin on DNA repair genes in common carp

The present study aimed to investigate the short-time (24 h) effect of aflatoxin B1 (AFB1) and sterigmatocystin (STC) on the expression of hsp70, p53, gadd45, and ogg1 genes in common carp hepatopancreas. Our results showed that aflatoxin B1 and sterigmatocystin can stimulate the expression of DNA repair genes, mainly by hour 24. This significant finding contributes to our understanding of the short-term effects of these mycotoxins on ogg1 genes in common carp hepatopancreas. One-year-old common carp juveniles were randomly distributed into five groups (Control, AFB1 0.4 mg kg−1 feed, STC1 1 mg kg−1 feed, STC2 2 mg kg−1 feed, and STC3 3 mg kg−1 feed). Hepatopancreas samples were collected three times (8, 16, and 24 h) in each group. No significant ogg1 and p53 expression changes were observed at 8 and 16 h after exposure. All measured genes were upregulated by the 24th hour in aflatoxin and STC3 groups. An increase in hsp70 gene expression was detected in all groups and all sampling. A significant decrease in gadd45aa gene expression was observed in the aflatoxin B1 group at hour 8. At hour 16, there was no significant change, while at hour 24, all treated groups were significantly different from the control. In summary, our results suggest that aflatoxin B1 and sterigmatocystin can stimulate the expression of DNA repair genes, mainly by hour 24. Further investigations are needed to get information about DNA damage parallel to the DNA repair mechanisms.

Oxidative DNA damage estimated by urinary 8-Hydroxy-2’ –Deoxyguanosine (8-OHdG) and 8-Oxoguanine DNA Glycosylase (OGG1) in cigarette and non-cigarette smokers in South West Nigeria

BACKGROUND: The thousands of chemicals and compounds found in cigarette smoke, including many free radicals and oxidants, can cause oxidative damage to DNA either directly or by producing reactive oxygen species in cultured cells. This study was carried out to analyze the urinary 8-Oxoguanine DNA Glycosylase (OGG1) and 8-Hydroxy-2’ –Deoxyguanosine (8-OHdG) among cigarette and non-cigarette smokers in South-West, Nigeria. METHODS: Urine samples were collected from 250 cigarette smokers and 200 non-cigarette smokers who live in south-west, Nigeria. Questionnaire was administered first to both cigarette and non-cigarette smokers prior to specimen collection. About 10mls of urine samples were collected from each of the subjects and was used to carry out Oxoguanine Glycosylase and 8-Hydroxyl-2-deoxyguanosine using spectrophotometer at 450 nm wavelength. RESULTS: There was a significant (P < 0.05) increase in Urinary 8-OHdG (345.84±90.98 vs 223±68.48) and OGG1 (220.71±59.55 vs 97.20±56.14) of the cigarette smokers when compared with that of non-cigarette smokers. CONCLUSION: On the basis of this study, it has been observed and established that indulging in cigarette smoking can result in oxidative stress and DNA damage.