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Mao-Wen Weng, Hyun-Wook Lee, Sung-Hyun Park, Yu Hu, Hsing-Tsui Wang, Lung-Chi Chen, William N Rom, William C Huang, Herbert Lepor, Xue-Ru Wu, Chung S Yang, Moon-Shong Tang
Tobacco smoke (TS) contains numerous cancer-causing agents, with polycyclic aromatic hydrocarbons (PAHs) and nitrosamines being most frequently cited as the major TS human cancer agents. Many lines of evidence seriously question this conclusion. To resolve this issue, we determined DNA adducts induced by the three major TS carcinogens: benzo( a )pyrene (BP), 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanoe (NNK), and aldehydes in humans and mice. In mice, TS induces abundant aldehyde-induced γ-hydroxy-propano-deoxyguanosine (γ-OH-PdG) and α-methyl-γ-OH-PdG adducts in the lung and bladder, but not in the heart and liver...
June 18, 2018: Proceedings of the National Academy of Sciences of the United States of America
Pilar Mur, Ann-Sofie Jemth, Luka Bevc, Nuno Amaral, Matilde Navarro, Rafael Valdés-Mas, Tirso Pons, Gemma Aiza, Miguel Urioste, Alfonso Valencia, Conxi Lázaro, Victor Moreno, Xose S Puente, Pål Stenmark, Ulrika Warpman-Berglund, Gabriel Capellá, Thomas Helleday, Laura Valle
The causal association of NUDT1 ( = MTH1) and OGG1 with hereditary colorectal cancer (CRC) remains unclear. Here we sought to provide additional evidence for or against the causal contribution of NUDT1 and OGG1 mutations to hereditary CRC and/or polyposis. Mutational screening was performed using pooled DNA amplification and targeted next generation sequencing in 529 families (441 uncharacterized MMR-proficient familial non-polyposis colorectal cancer and 88 polyposis cases). Co-segregation, in silico analyses, in vitro functional assays and case-control associations, were carried out to characterize the identified variants...
June 13, 2018: Human Mutation
Henri Johannes Haapanen, Johanna Herajärvi, Hannu-Pekka Honkanen, Caius Mustonen, Hannu Tuominen, Ulla Puistola, Vesa Anttila, Tatu Juvonen
In experimental settings, remote ischemic preconditioning (RIPC) has shown a positive effect regarding spinal cord protection after local ischemia. In this study, we conducted spinal cord immunohistochemistry to demonstrate the protective effect of RIPC after 24 hours of the regional ischemia. Methods: Twenty piglets were randomized into an RIPC group (n = 10) and a control group (n = 10). The RIPC group underwent transient left hind limb ischemia before systematic left subclavian artery and segmental artery occlusion at the level of the diaphragm...
May 29, 2018: Heart Surgery Forum
Sambuddha Das, Sukanya Purkayastha, Hirakjyoti Roy, Anima Sinha, Yashmin Choudhury
We investigated the effect of polymorphisms in four DNA repair genes, viz. RAD18 Arg302Gln (G>A) (rs373572), XPD Asp312Asn (G>A) (rs1799793), APE1 Asp148Glu (T>G) (rs3136820), and OGG1 Ser326Cys (C>G) (rs1052133) on the risk for type 2 diabetes mellitus (T2DM) and hypertension (HT) in association with smoking, tobacco chewing, and alcohol consumption in a population from Northeast India. The study subjects were comprised of 70 patients suffering from both T2DM and HT and 83 healthy controls. Genotyping was performed using ARMS-PCR for XPD Asp312Asn (G>A) and PCR-CTPP for RAD18 Arg302Gln (G>A), APE1 Asp148Glu (T>G) and OGG1 Ser326Cys (C>G)...
June 9, 2018: Biomolecular Concepts
Beverly A Baptiste, Steven R Katchur, Elayne M Fivenson, Deborah L Croteau, William L Rumsey, Vilhelm A Bohr
The common oxidatively generated lesion, 8-oxo-7,8-dihydroguanine (8-oxoGua), is removed from DNA by base excision repair. The glycosylase primarily charged with recognition and removal of this lesion is 8-oxoGuaDNA glycosylase 1 (OGG1). When left unrepaired, 8-oxodG alters transcription and is mutagenic. Individuals homozygous for the less active OGG1 allele, Ser326Cys, have increased risk of several cancers. Here, small molecule enhancers of OGG1 were identified and tested for their ability to stimulate DNA repair and protect cells from the environmental hazard paraquat (PQ)...
June 4, 2018: Free Radical Biology & Medicine
Johanna H K Kauppila, Nina A Bonekamp, Arnaud Mourier, Marita A Isokallio, Alexandra Just, Timo E S Kauppila, James B Stewart, Nils-Göran Larsson
Mitochondrial DNA (mtDNA) mutations become more prevalent with age and are postulated to contribute to the ageing process. Point mutations of mtDNA have been suggested to originate from two main sources, i.e. replicative errors and oxidative damage, but the contribution of each of these processes is much discussed. To elucidate the origin of mtDNA mutations, we measured point mutation load in mice with deficient mitochondrial base-excision repair (BER) caused by knockout alleles preventing mitochondrial import of the DNA repair glycosylases OGG1 and MUTYH (Ogg1 dMTS, Mutyh dMTS)...
May 31, 2018: Nucleic Acids Research
Debora Lia, Aurelio Reyes, Julliane Tamara Araújo de Melo Campos, Tristan Piolot, Jan Baijer, J Pablo Radicella, Anna Campalans
Accumulation of 8-oxoG in mtDNA and mitochondrial dysfunction have been observed in cells deficient for the DNA glycosylase OGG1 exposed to oxidative stress. In human cells up to eight mRNAs for OGG1 can be generated by alternative splicing and it is still unclear which of them codes for the protein that ensures the repair of 8-oxoG in mitochondria. Here, we show that the α-OGG1 isoform, considered up to now to be exclusively nuclear, has a functional mitochondrial targeting signal and is imported in mitochondria...
May 30, 2018: Journal of Cell Science
Hossein Behboudi, Sakineh Kazemi Noureini, Tooba Ghazanfari, Sussan K Ardestani
Sulfur mustard (SM) is a vesicant chemical warfare agent, and a very potent alkylating agent. SM exerts its cytotoxicity via direct alkylation of biomacromolecules, and overproduction of reactive oxygen species (ROS). Previous studies have shown that SM-induced oxidative stress has adverse effects on antioxidant defense system, and damages lipids and proteins. The aim of this study was to investigate the effect of SM-induced oxidative stress on DNA damage, and cellular senescence in SM-exposed victims. For this purpose, MDA levels as a measure of oxidative stress in the serum, 8-oxo-dG content of the genomic DNA, and OGG1 expression as two biomarkers of oxidative DNA damage, as well as, telomere length, and p16INK4a expression as two biomarkers of cellular senescence were measured in the peripheral blood leukocytes of 215 males who were exposed to SM 20 to 25 years ago, and 53 unexposed healthy males as the control group...
May 23, 2018: International Immunopharmacology
Ruoxi Wang, Chunshuang Li, Ping Qiao, Yaoyao Xue, Xu Zheng, Hongyu Chen, Xianlu Zeng, Wenguang Liu, Istvan Boldogh, Xueqing Ba
Oxidative stress-induced DNA damage has been well acknowledged as a major cause leading to cell death, which is etiologically linked to ischemic injury and degenerative alterations. The most common oxidation product of DNA is base lesion 8-oxo-7,8-dihydroguanine (8-oxoG), which is repaired by 8-oxoG glycosylase1 (OGG1)-initiated baseexcision repair (BER) pathway (OGG1-BER); however, the role of OGG1-BER in oxidative stress-induced cell death is poorly investigated. DNA strand breaks and apurinic/apyrimidinic (AP) sites are effective substrates to activate DNA damage sensor poly(ADP-ribose) polymerase 1 (PARP1)...
May 24, 2018: Cell Death & Disease
Jacek Kabzinski, Anna Walczak, Adam Dziki, Michał Mik, Ireneusz Majsterek
As a result of reactive oxygen species operation, cell damage occurs in both cellular organelles and molecules, including DNA. Oxidative damage within the genetic material can lead to accumulation of mutations and consequently to cancer transformation. OGG1 glycosylase, a component of the Base Excision Repair (BER) system, is one of the enzymes that prevents excessive accumulation of 8-oxoguanine (8-oxG), the most common compound formed by oxidative DNA damage. In case of structural changes of OGG1 resulting from polymorphic variants, we can observe a significant increase in the concentration of 8-oxG...
April 30, 2018: Polski Przeglad Chirurgiczny
Lavinia Tinaburri, Mariarosaria D'Errico, Sara Sileno, Riccardo Maurelli, Paolo Degan, Alessandra Magenta, Elena Dellambra
Oxidative DNA damage accumulation may induce cellular senescence. Notably, senescent cells accumulate in aged tissues and are present at the sites of age-related pathologies. Although the signaling of DNA strand breaks has been extensively studied, the role of oxidative base lesions has not fully investigated in primary human keratinocyte aging. In this study, we show that primary human keratinocytes from elderly donors are characterized by a significant accumulation of the oxidative base lesion 8-OH-dG, impairment of oxidative DNA repair, and increase of miR-200a levels...
2018: Oxidative Medicine and Cellular Longevity
Vivian F Silva Kahl, Fernanda Rabaioli da Silva, Jodel da Silva Alves, Gabrieli Flesch da Silva, Juliana Picinini, Varinderpal Singh Dhillon, Michael Fenech, Melissa Rosa de Souza, Johnny F Dias, Claudia Telles de Souza, Mirian Salvador, Cátia Dos Santos Branco, Flávia Valadão Thiesen, Daniel Simon, Juliana da Silva
Tobacco farming has been proving to induce poor health outcomes in agricultural workers, genomic instability being the triggering one. This study evaluated influence of PON1 (paraoxonase 1), SOD2 (superoxide dismutase), OGG1 (8-oxoguanine glycosylase), XRCC1 (X-ray repair cross-complementing protein 1), and XRCC4 (X-ray repair cross-complementing protein 4) genes polymorphisms on DNA damage in 121 subjects occupationally exposed to pesticides mixtures and nicotine at tobacco fields and 121 non-exposed individuals...
September 15, 2018: Ecotoxicology and Environmental Safety
Nanami Gotoh, Takayuki Saitoh, Noriyuki Takahashi, Tetsuhiro Kasamatsu, Yusuke Minato, Alkebsi Lobna, Tsukasa Oda, Takumi Hoshino, Toru Sakura, Hiroaki Shimizu, Makiko Takizawa, Hiroshi Handa, Akihiko Yokohama, Norifumi Tsukamoto, Hirokazu Murakami
Recent studies have shown that tumors of relapsed acute myeloid leukemia (AML) present additional genetic mutations compared to the primary tumors. The base excision repair (BER) pathway corrects oxidatively damaged mutagenic bases and plays an important role in maintaining genetic stability. The purpose of the present study was to investigate the relationship between BER functional polymorphisms and AML relapse. We focused on five major polymorphisms: OGG1 S326C, MUTYH Q324H, APE1 D148E, XRCC1 R194W, and XRCC1 R399Q...
May 8, 2018: International Journal of Hematology
Yan Wang, Xiaohui Sun, Lianying Fang, Keqiu Li, Ping Yang, Liqing Du, Kaihua Ji, Jinhan Wang, Qiang Liu, Chang Xu, Guang Li, John P Giesy, Markus Hecker
BACKGROUND: Managing and recycling electronic waste (e-waste), while useful and necessary, has resulted in significant contamination of several environments in China. The area around Tianjin, China has become one of the world's largest e-waste disposal centers, where electronics are processed by manually disassembly or burning, which can result in serious exposure of workers to a multitude of toxicants. OBJECTIVE: The present study assessed potential genomic damage in workers involved in recycling e-waste...
May 1, 2018: Environment International
Tao Wang, Haitao Wang, Suisheng Yang, Hongyun Guo, Binming Zhang, Huan Guo, Lan Wang, Gongjian Zhu, Yongdong Zhang, Haihong Zhou, Xiuli Zhang, Haining Li, Haixiang Su
BACKGROUND: Genetic variations in key DNA repair genes may influence DNA repair capacity, DNA damage and breast carcinogenesis. The current study aimed to estimate the association of APEX1 and OGG1 polymorphisms with the risk of breast cancer development. METHODS: A total of 518 patients with histopathologically confirmed breast cancer and 921 region- and age-matched cancer-free controls were genotyped for the APEX1 polymorphisms rs3136817 and rs1130409 and the OGG1 polymorphisms rs1052133 and rs2072668 using a QuantStudio™ 12 K Flex Real-Time PCR System...
May 2, 2018: BMC Medical Genetics
Samantha M Anderson, Rajen N Naidoo, Prithiksha Ramkaran, Kareshma Asharam, Sheena Muttoo, Anil A Chuturgoon
The global HIV and obesity epidemics are major public health concerns; particularly as both are associated with increased risk of adverse birth outcomes. Despite extensive research, their combined effect, in terms of birth outcomes, has not been investigated. A single-nucleotide polymorphism (SNP) within 8-oxoguanine glycosylase 1 (OGG1) (Ser326Cys) has been suggested to affect body mass indices and therefore could predispose South African (SA) women to adverse effects of obesity. This study investigated the associations of OGG1 Ser326Cys SNP in relation to HIV and obesity on the susceptibility of low-birthweight (LBW) and pre-term birth (PTB) in SA women exposed to ambient air-pollution living in Durban...
April 27, 2018: Reproductive Toxicology
Mei Yang, Junfang Zhang, Shu Su, Bai Qin, Lihua Kang, Rongrong Zhu, Huaijin Guan
PURPOSE: Age-related cataract (ARC) is a leading cause of visual impairment and blindness worldwide. DNA damage and malfunction of DNA repair are believed to contribute to the pathogenesis of ARC. Aside from increasing age, the risk factors for ARC appear to be rather complex, and one or more gene variations could play critical roles in the diverse processes of ARC progression. This study aimed to investigate the combined effects of different genetic variants on ARC risk. METHODS: A cohort of 789 ARC patients and 531 normal controls from the Jiangsu Eye Study was included in this study...
2018: PloS One
Abram B Kamiza, Ling-Ling Hsieh, Reiping Tang, Huei-Tzu Chien, Chih-Hsiung Lai, Li-Ling Chiu, Tsai-Ping Lo, Kuan-Yi Hung, Jeng-Fu You, Wen-Chang Wang, Chao A Hsiung, Chih-Ching Yeh
BACKGROUND: DNA repair genes are crucial for maintaining genomic stability by preventing mutagenesis and carcinogenesis. The present retrospective cohort study aimed at investigating whether MLH1, APEX1, MUTYH, OGG1, NUDT1, XRCC5, XPA, and ERCC2 single nucleotide polymorphisms (SNPs) are associated with colorectal cancer (CRC) in Chinese population with Lynch syndrome. METHODS: From Amsterdam criteria family registry, we identified 270 patients with Lynch syndrome...
April 17, 2018: Molecular Genetics & Genomic Medicine
Aarti Shah, Kelly Gray, Nichola Figg, Alison Finigan, Lakshi Starks, Martin Bennett
Background -Atherosclerotic plaques demonstrate extensive accumulation of oxidative DNA damage, predominantly as 8-oxoguanine (8oxoG) lesions. 8oxoG is repaired by base excision repair (BER) enzymes; however, the mechanisms regulating 8oxoG accumulation in vascular smooth muscle cells (VSMCs) and its effects on their function and in atherosclerosis are unknown. Methods -We studied levels of 8oxoG and its regulatory enzymes in human atherosclerosis, the mechanisms regulating 8oxoG repair and the BER enzyme 8oxoG DNA glycosylase I (OGG1) in VSMCs in vitro, and the effects of reducing 8oxoG in VSMCs in atherosclerosis in ApoE-/- mice...
April 11, 2018: Circulation
Deniz Ceylan, Gamze Tuna, Güldal Kirkali, Zeliha Tunca, Güneş Can, Hidayet Ece Arat, Melis Kant, Miral Dizdaroglu, Ayşegül Özerdem
Oxidatively-induced DNA damage has previously been associated with bipolar disorder. More recently, impairments in DNA repair mechanisms have also been reported. We aimed to investigate oxidatively-induced DNA lesions and expression of DNA glycosylases involved in base excision repair in euthymic patients with bipolar disorder compared to healthy individuals. DNA base lesions including both base and nucleoside modifications were measured using gas chromatography-tandem mass spectrometry and liquid chromatography-tandem mass spectrometry with isotope-dilution in DNA samples isolated from leukocytes of euthymic patients with bipolar disorder (n = 32) and healthy individuals (n = 51)...
May 2018: DNA Repair
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