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https://www.readbyqxmd.com/read/29431562/ionizing-radiation-does-not-impair-the-mechanisms-controlling-genetic-stability-during-t-cell-receptor-gene-rearrangement-in-mice
#1
Serge M Candéias, Sylwia Kabacik, Ann-Karin Olsen, Dag M Eide, Dag A Brede, Simon Bouffler, Christophe Badie
PURPOSE: To determine whether low dose/low dose rate radiation-induced genetic instability may result from radiation-induced inactivation of mechanisms induced by the ATM-dependent DNA damage response checkpoint. To this end, we analysed the faithfulness of T cell receptor (TR) gene rearrangement by V(D)J recombination in DNA from mice exposed to a single dose of X-ray or chronically exposed to low dose rate γ radiation. MATERIALS AND METHODS: Genomic DNA obtained from the blood or the thymus of wild type or Ogg1-deficient mice exposed to low (0...
February 12, 2018: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/29409673/ogg1-regulates-the-level-of-symmetric-dimethylation-of-histone-h4-arginine-3-by-interacting-with-prmt5
#2
Xiaolong Zhou, Wentao Wang, Chengtao Du, Feifei Yan, Songbai Yang, Ke He, Han Wang, Ayong Zhao
OGG1 is the first enzyme in the base excision repair pathway (BER) responsible for repairing 8-oxoguanine DNA lesions. Recent studies found that OGG1 may also be involved in epigenetic regulation. In this study, we focused on the roles of OGG1 in histone modification. First, to study the effects of OGG1 on histone modification, the protein levels of symmetric dimethylation of histone H4 arginine-3 (H4R3me2s) were determined by western blot analysis following the knockdown or overexpression of OGG1. Second, the molecular mechanisms by which OGG1 regulates H4R3me2s were assessed by co-immunoprecipitation (CO-IP) assays in mouse embryonic fibroblast (MEF) wild-type (WT) and Ogg-/- cells...
February 2, 2018: Molecular and Cellular Probes
https://www.readbyqxmd.com/read/29378943/e-cigarette-smoke-damages-dna-and-reduces-repair-activity-in-mouse-lung-heart-and-bladder-as-well-as-in-human-lung-and-bladder-cells
#3
Hyun-Wook Lee, Sung-Hyun Park, Mao-Wen Weng, Hsiang-Tsui Wang, William C Huang, Herbert Lepor, Xue-Ru Wu, Lung-Chi Chen, Moon-Shong Tang
E-cigarette smoke delivers stimulant nicotine as aerosol without tobacco or the burning process. It contains neither carcinogenic incomplete combustion byproducts nor tobacco nitrosamines, the nicotine nitrosation products. E-cigarettes are promoted as safe and have gained significant popularity. In this study, instead of detecting nitrosamines, we directly measured DNA damage induced by nitrosamines in different organs of E-cigarette smoke-exposed mice. We found mutagenic O6-methyldeoxyguanosines and γ-hydroxy-1,N2 -propano-deoxyguanosines in the lung, bladder, and heart...
January 29, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29376367/potent-and-selective-inhibitors-of-8-oxoguanine-dna-glycosylase-ogg1
#4
Yu-Ki Tahara, Douglas Auld, Debin Ji, Andrew A Beharry, Anna M Kietrys, David L Wilson, Marta Jimenez, Daniel King, Zachary Nguyen, Eric T Kool
The activity of DNA repair enzyme OGG1, which excises oxidized base 8-oxoguanine (8-OG) from DNA, is closely linked to mutagenesis, genotoxicity, cancer, and inflammation. To test the roles of OGG1-mediated repair in these pathways, we have undertaken the development of noncovalent small-molecule inhibitors of the enzyme. Screening of a PubChem-annotated library using a recently developed fluorogenic 8-oxoguanine excision assay resulted in multiple validated hit structures, including selected lead hit tetrahydroquinoline 1 (IC50 = 1...
January 27, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29367705/somatic-apc-mosaicism-and-oligogenic-inheritance-in-genetically-unsolved-colorectal-adenomatous-polyposis-patients
#5
Michele Ciavarella, Sara Miccoli, Anna Prossomariti, Tommaso Pippucci, Elena Bonora, Francesco Buscherini, Flavia Palombo, Roberta Zuntini, Tiziana Balbi, Claudio Ceccarelli, Franco Bazzoli, Luigi Ricciardiello, Daniela Turchetti, Giulia Piazzi
Germline variants in the APC gene cause familial adenomatous polyposis. Inherited variants in MutYH, POLE, POLD1, NTHL1, and MSH3 genes and somatic APC mosaicism have been reported as alternative causes of polyposis. However, ~30-50% of cases of polyposis remain genetically unsolved. Thus, the aim of this study was to investigate the genetic causes of unexplained adenomatous polyposis. Eight sporadic cases with >20 adenomatous polyps by 35 years of age or >50 adenomatous polyps by 55 years of age, and no causative germline variants in APC and/or MutYH, were enrolled from a cohort of 56 subjects with adenomatous colorectal polyposis...
January 24, 2018: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/29359425/mechanism-underlying-the-effect-of-long-term-exposure-to-low-dose-of-pesticides-on-dna-integrity
#6
Renata Alleva, Nicola Manzella, Simona Gaetani, Tiziana Bacchetti, Massimo Bracci, Veronica Ciarapica, Federica Monaco, Battista Borghi, Monica Amati, Gianna Ferretti, Marco Tomasetti
Pesticides, including herbicides, insecticides and fungicides, are widely used in intensive agriculture. Recently, the long-term effects of pesticide exposure were found to be associated with many diseases. In this study, we evaluated the long-term effect of low-level exposure to a mixture of pesticides on DNA damage response (DDR) in relation to individual detoxifying variability. A residential population chronically exposed to pesticides was enrolled, biological/environmental pesticide levels; paroxonase 1 (PON-1) activity and 192 Q/R polymorphism and DDR were evaluated at three different periods of pesticide exposure...
January 23, 2018: Environmental Toxicology
https://www.readbyqxmd.com/read/29336731/lead-induces-dna-damage-and-alteration-of-alad-and-antioxidant-genes-mrna-expression-in-construction-site-workers
#7
Zertashia Akram, Sadaf Riaz, Mahmood Akhtar Kayani, Sarwat Jahan, Malik Waqar Ahmad, Muhammad Abaid Ullah, Hizbullah Wazir, Ishrat Mahjabeen
Oxidative stress and DNA damage are considered as possible mechanism involved in lead toxicity. To test this hypothesis, DNA damage and expression variations of ALAD, SOD2 and OGG1-2░a genes was studied in a cohort of 100 exposed workers and 100 controls with comet assay and real-time PCR. Results indicated that increased number of comets was observed in exposed workers versus controls (p<0.001). After qPCR analysis, significant down-regulation in ALAD (p<0.0001), SOD2 (p<0.0001) and OGG1-2░a (p<0...
January 16, 2018: Archives of Environmental & Occupational Health
https://www.readbyqxmd.com/read/29306194/downregulation-of-parp1-transcription-by-cdk4-6-inhibitors-sensitizes-human-lung-cancer-cells-to-anticancer-drug-induced-death-by-impairing-ogg1-dependent-base-excision-repair
#8
Dominika Tempka, Paulina Tokarz, Kinga Chmielewska, Magdalena Kluska, Julita Pietrzak, Żaneta Rygielska, László Virág, Agnieszka Robaszkiewicz
Hallmarks of cancer cells include uncontrolled growth and rapid proliferation; thus, cyclin-dependent kinases are a therapeutic target for cancer treatment. Treating non-small lung cancer cells with sublethal concentrations of the CDK4/6 inhibitors, ribociclib (LEE011) and palbociclib (PD0332991), which are approved by the FDA for anticancer therapies, caused cell cycle arrest in the G1 phase and suppression of poly(ADP-ribose) polymerase 1 (PARP1) transcription by inducing recruitment of the RB1-E2F1-HDAC1-EZH2 repressive complex to the PARP1 promoter...
December 29, 2017: Redox Biology
https://www.readbyqxmd.com/read/29305132/the-mediterranean-diet-the-ogg1-gene-and-disease-risk-early-evidence
#9
Nancy J Emenaker, Ashley J Vargas
No abstract text is available yet for this article.
January 2, 2018: Journal of the Academy of Nutrition and Dietetics
https://www.readbyqxmd.com/read/29305130/effects-of-the-ser326cys-polymorphism-in-the-dna-repair-ogg1-gene-on-cancer-cardiovascular-and-all-cause-mortality-in-the-predimed-study-modulation-by-diet
#10
Dolores Corella, Judith B Ramírez-Sabio, Oscar Coltell, Carolina Ortega-Azorín, Ramón Estruch, Miguel A Martínez-González, Jordi Salas-Salvadó, José V Sorlí, Olga Castañer, Fernando Arós, Franscisco J Garcia-Corte, Lluís Serra-Majem, Enrique Gómez-Gracia, Miquel Fiol, Xavier Pintó, Guillermo T Saez, Estefanía Toledo, Josep Basora, Montserrat Fitó, Montserrat Cofán, Emilio Ros, Jose M Ordovas
BACKGROUND: Oxidatively induced DNA damage, an important factor in cancer etiology, is repaired by oxyguanine glycosylase 1 (OGG1). The lower repair capacity genotype (homozygote Cys326Cys) in the OGG1-rs1052133 (Ser326Cys) polymorphism has been associated with cancer risk. However, no information is available in relation to cancer mortality, other causes of death, and modulation by diet. OBJECTIVE: Our aim was to evaluate the association of the OGG1-rs1052133 with total, cancer, and cardiovascular disease (CVD) mortality and to analyze its modulation by the Mediterranean diet, focusing especially on total vegetable intake as one of the main characteristics of this diet...
January 2, 2018: Journal of the Academy of Nutrition and Dietetics
https://www.readbyqxmd.com/read/29296039/modulation-of-radiation-induced-base-excision-repair-pathway-gene-expression-by-melatonin
#11
Saeed Rezapoor, Alireza Shirazi, Sakineh Abbasi, Javad Tavakkoly Bazzaz, Pantea Izadi, Hamed Rezaeejam, Majid Valizadeh, Farid Soleimani-Mohammadi, Masoud Najafi
Objective: Approximately 70% of all cancer patients receive radiotherapy. Although radiotherapy is effective in killing cancer cells, it has adverse effects on normal cells as well. Melatonin (MLT) as a potent antioxidant and anti-inflammatory agent has been proposed to stimulate DNA repair capacity. We investigated the capability of MLT in the modification of radiation-induced DNA damage in rat peripheral blood cells. Materials and Methods: In this experimental study, male rats (n = 162) were divided into 27 groups (n = 6 in each group) including: irradiation only, vehicle only, vehicle with irradiation, 100 mg/kg MLT alone, 100 mg/kg MLT plus irradiation in 3 different time points, and control...
October 2017: Journal of Medical Physics
https://www.readbyqxmd.com/read/29289706/an-engineered-cell-line-lacking-ogg1-and-mutyh-glycosylases-implicates-the-accumulation-of-genomic-8-oxoguanine-as-the-basis-for-paraquat-mutagenicity
#12
Preechaya Tajai, Bogdan I Fedeles, Tawit Suriyo, Panida Navasumrit, Jantamas Kanitwithayanun, John M Essigmann, Jutamaad Satayavivad
Paraquat (1,1'-dimethyl, 4,4'-bipyridinium dichloride; PQ), a widely used herbicide, is toxic to mammals through ingestion, inhalation and skin contact. Epidemiological data suggest that PQ is also mutagenic and carcinogenic, especially in high doses. The toxic and mutagenic properties of PQ are attributed to the ability of the molecule to redox-cycle, which generates reactive oxygen species (ROS) and subsequent oxidative stress. ROS also cause oxidative DNA damage such as 8-oxoguanine (8OG), a mutagenic base that, when replicated, causes G to T transversion mutations...
December 28, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29227732/%C3%AE-8-oxoguanine-dna-glycosylase-overexpression-reduces-oxidative-stress-induced-mitochondrial-dysfunction-and-apoptosis-through-the-jnk-signaling-pathway-in-human-bronchial-epithelial-cells
#13
Ziying Lin, Wenya Xu, Chunyan Li, Yahong Wang, Lawei Yang, Bao'an Zou, Shenglan Gao, Weimin Yao, Zeqing Song, Gang Liu
8-Oxoguanine DNA glycosylase (OGG1) is responsible for repairing 8-oxo-7,8-dihydroguanine (8-oxoG). Our previous study demonstrated that α-OGG1 protects cells from oxidative damage-induced apoptosis and mitochondrial dysfunction in human lung cancer cells. However, the function of β-OGG1 remains to be elucidated. In this study, we demonstrated that overexpressed β-OGG1 has the same role as α-OGG1 in protecting human bronchial epithelial cells from apoptosis and mitochondrial dysfunction. Furthermore, flow cytometry, confocal microscopy, and western blotting showed that the overexpression of β-OGG1 could block oxidant-induced apoptosis in human bronchial epithelial cells...
December 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/29209987/genetic-investigation-of-polymorphic-ogg1-and-mutyh-genes-towards-increased-susceptibility-in-lung-adenocarcinoma-and-its-impact-on-overall-survival-of-lung-cancer-patients-treated-with-platinum-based-chemotherapy
#14
Amrita Singh, Navneet Singh, Digambar Behera, Siddharth Sharma
Genes OGG1 and MUTYH are the two primary genes in Base excision repair pathway. OGG1 hydrolyzes the sugar phosphate backbone and remove the damaged base creating abasic site. MUTYH complements OGG1 as it particularly remove adenine mispaired with 8-oxo-G. Both OGG1 and MUTYH act as a check for the mis-incorporation of bases may be due to damages incurred on DNA. DNA isolation for 326 lung cancer cases and 330 controls was followed by genotyping making use of PCR-RFLP. Logistic regression was done to analyze the risk towards lung cancer...
December 5, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/29207315/8-oxoguanine-dna-glycosylase-ogg1-controls-hepatic-gluconeogenesis
#15
Katja Scheffler, Lyudmila Rachek, Panpan You, Alexander D Rowe, Wei Wang, Anna Kuśnierczyk, Lene Kittelsen, Magnar Bjørås, Lars Eide
Mitochondrial DNA (mtDNA) resides in close proximity to metabolic reactions, and is maintained by the 8-oxoguanine DNA glycosylase (Ogg1) and other members of the base excision repair pathway. Here, we tested the hypothesis that changes in liver metabolism as under fasting/feeding conditions would be sensed by liver mtDNA, and that Ogg1 deficient mice might unravel a metabolic phenotype. Wild type (WT) and ogg1-/- mice were either fed ad libitum or subjected to fasting for 24h, and the corresponding effects on liver gene expression, DNA damage, as well as serum values were analyzed...
November 28, 2017: DNA Repair
https://www.readbyqxmd.com/read/29165690/the-regulatory-g4-motif-of-the-kirsten-ras-kras-gene-is-sensitive-to-guanine-oxidation-implications-on-transcription
#16
Susanna Cogoi, Annalisa Ferino, Giulia Miglietta, Erik B Pedersen, Luigi E Xodo
KRAS is one of the most mutated genes in human cancer. It is controlled by a G4 motif located upstream of the transcription start site. In this paper, we demonstrate that 8-oxoguanine (8-oxoG), being more abundant in G4 than in non-G4 regions, is a new player in the regulation of this oncogene. We designed oligonucleotides mimicking the KRAS G4-motif and found that 8-oxoG impacts folding and stability of the G-quadruplex. Dimethylsulphate-footprinting showed that the G-run carrying 8-oxoG is excluded from the G-tetrads and replaced by a redundant G-run in the KRAS G4-motif...
November 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29145655/paternal-exposure-to-environmental-chemical-stress-affectsmale-offspring-s-hepatic-mitochondria
#17
Roger Godschalk, Alex Remels, Camiel Hoogendoorn, Jan van Benthem, Mirjam Luijten, Nur Duale, Gunnar Brunborg, Ann-Karin Olsen, Freek G Bouwman, Armelle Munnia, Marco Peluso, Edwin Mariman, Frederik Jan van Schooten
Pre-conceptional paternal exposures may affect offspring's health, which cannot be explained by mutations in germ cells, but by persistent changes in the regulation of gene expression. Therefore, we investigated whether pre-conceptional paternal exposure to benzo[a]pyrene (B[a]P) could alter the offspring's phenotype. Male C57BL/6 mice were exposed to B[a]P by gavage for 6 weeks, 3x per week, and were crossed with unexposed BALB-c females 6 weeks after the final exposure. The offspring was kept under normal feeding conditions and was sacrificed at 3 weeks of age...
November 14, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29139108/a-3-untranslated-region-polymorphism-rs2304277-in-the-dna-repair-pathway-gene-ogg1-is-a-novel-risk-modulator-for-urothelial-bladder-carcinoma
#18
Tayyaba Ahmed, Saira Nawaz, Rabia Noreen, Kashif Sardar Bangash, Abdur Rauf, Muhammad Younis, Khursheed Anwar, Muhammad Athar Khawaja, Maleeha Azam, Abid Ali Qureshi, Saeed Akhter, Lambertus A Kiemeney, Raheel Qamar, Syeda Hafiza Benish Ali
Altered DNA repair capacity may affect an individual's susceptibility to cancers due to compromised genomic integrity. This study was designed to elucidate the association of selected polymorphisms in DNA repair genes with urothelial bladder carcinoma (UBC). OGG1 rs1052133 and rs2304277, XRCC1 rs1799782 and rs25487, XRCC3 rs861539, XPC rs2228001, and XPD rs13181 were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 200 UBC cases and 200 controls. We found association of OGG1 rs2304277 [odds ratio (OR)GG = 3...
November 15, 2017: Annals of Human Genetics
https://www.readbyqxmd.com/read/29133960/divergent-roles-for-clusterin-in-lung-injury-and-repair
#19
David M Habiel, Ana Camelo, Milena Espindola, Timothy Burwell, Richard Hanna, Elena Miranda, Alan Carruthers, Matthew Bell, Ana Lucia Coelho, Hao Liu, Fernanda Pilataxi, Lori Clarke, Ethan Grant, Arthur Lewis, Bethany Moore, Darryl A Knight, Cory M Hogaboam, Lynne A Murray
Lung fibrosis is an unabated wound healing response characterized by the loss and aberrant function of lung epithelial cells. Herein, we report that extracellular Clusterin promoted epithelial cell apoptosis whereas intracellular Clusterin maintained epithelium viability during lung repair. Unlike normal and COPD lungs, IPF lungs were characterized by significantly increased extracellular Clusterin whereas the inverse was evident for intracellular Clusterin. In vitro and in vivo studies demonstrated that extracellular Clusterin promoted epithelial cell apoptosis while intercellular Clusterin modulated the expression of the DNA repair proteins, MSH2, MSH6, OGG1 and BRCA1...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29129468/inhibition-of-rac1-ameliorates-neuronal-oxidative-stress-damage-via-reducing-bcl-2-rac1-complex-formation-in-mitochondria-through-pi3k-akt-mtor-pathway
#20
Yundan Pan, Na Wang, Pingping Xia, E Wang, Qulian Guo, Zhi Ye
Although the neuroprotective effects of Rac1 inhibition have been reported in various cerebral ischemic models, the molecular mechanisms of action have not yet been fully elucidated. In this study, we investigated whether the inhibition of Rac1 provided neuroprotection in a diabetic rat model of focal cerebral ischemia and hyperglycemia-exposed PC-12 cells. Intracerebroventricular administration of lentivirus expressing the Rac1 small hairpin RNA (shRNA) and specific Rac1 inhibitor NSC23766 not only decreased the infarct volumes and improved neurologic deficits with a correlated significant activation of mitochondrial DNA specific proteins, such as OGG1 and POLG, but also elevated Bcl-2 S70 phosphorylation in mitochondria...
November 10, 2017: Experimental Neurology
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