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https://www.readbyqxmd.com/read/28640454/direct-quantification-of-gamma-h2ax-by-cell-based-high-throughput-screening-for-evaluation-of-genotoxicity-of-pesticides-in-a-human-thyroid-cell-lines
#1
Jerome M Hershman, Bryan France, Kevin Hon, Robert Damoiseaux
Genotoxicity is thought to be the cause of many cancers. Genotoxicity due to environmental toxins may be partly responsible for the dramatic increase in the incidence of papillary thyroid cancer over the past two decades. Here, we present a fully automatable assay platform that directly quantifies the phosphorylation of nuclear histone gamma H2AX (γH2AX), a specific cellular marker for DNA double strand breaks (DSBs) via immunohistochemistry and laser scanning cytometry. It multiplexes γH2AX with total cell number measured as propidium iodide and calculates the percentage of cells with DSBs...
June 22, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28612525/-the-role-of-dna-double-strain-damage-repairing-mechanisms-in-diabetic-atheroscolersis
#2
Li Zeng, Qun-Fang Ding, Ting-Yuan Xu, Fang Luo, Ning Ge, Shi-Tong Li
OBJECTIVES: To identify the role of DNA double-strain damage repairing pathway in the development of diabetics atherosclerosis. METHODS: Wistar male rats were randomly divided into three groups: control group (group A), balloon injury group (group B) and diabetes + balloon injury group (group C). Streptozotocin (STZ) was injected into rat abdomen to induce diabetes. After stabilizing high glucose, rats in group B and group C were both under aortic balloon injury technique and fed high lipid forage post-operatively...
March 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28565765/pravastatin-reduces-radiation-induced-damage-in-normal-tissues
#3
Hiroshi Doi, Seiji Matsumoto, Soichi Odawara, Toshiyuki Shikata, Kazuhiro Kitajima, Masao Tanooka, Yasuhiro Takada, Tohru Tsujimura, Norihiko Kamikonya, Shozo Hirota
Pravastatin is an inhibitor of 3-hydroxy-3-methyl- glutaryl-coenzyme A reductase that has been reported to have therapeutic applications in a range of inflammatory conditions. The aim of the present study was to assess the radioprotective effects of pravastatin in an experimental animal model. Mice were divided into two groups: The control group received ionizing radiation with no prior medication, while the pravastatin group received pravastatin prior to ionizing radiation. Pravastatin was administered orally at 30 mg/kg body weight in drinking water at 24 and 4 h before irradiation...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28494285/effects-of-in-situ-exposure-to-tritiated-natural-environments-a-multi-biomarker-approach-using-the-fathead-minnow-pimephales-promelas
#4
B Gagnaire, C Adam-Guillermin, A Festarini, I Cavalié, C Della-Vedova, C Shultz, S B Kim, H Ikert, C Dubois, S Walsh, F Farrow, D Beaton, E Tan, K Wen, M Stuart
Aquatic ecosystems are chronically exposed to radionuclides as well as other pollutants. Increased concentrations of pollutants in aquatic environments can present a risk to exposed organisms, including fish. The goal of this study was to characterize the effects of tritium, in the context of natural environments, on the health of fathead minnow, Pimephales promelas. Fish were exposed to tritium (activity concentrations ranging from 2 to 23,000Bq/L) and also to various concentrations of several metals to replicate multiple-stressor environments...
December 1, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28487501/oocyte-exposure-to-zno-nanoparticles-inhibits-early-embryonic-development-through-the-%C3%AE-h2ax-and-nf-%C3%AE%C2%BAb-signaling-pathways
#5
Jing Liu, Yong Zhao, Wei Ge, Pengfei Zhang, Xinqi Liu, Weidong Zhang, Yanan Hao, Shuai Yu, Lan Li, Meiqiang Chu, Lingjiang Min, Hongfu Zhang, Wei Shen
The impacts of zinc oxide nanoparticles on embryonic development following oocyte stage exposure are unknown and the underlying mechanisms are sparsely understood. In the current investigation, intact nanoparticles were detected in ovarian tissue in vivo and cultured cells in vitro under zinc oxide nanoparticles treatment. Zinc oxide nanoparticles exposure during the oocyte stage inhibited embryonic development. Notably, in vitro culture data closely matched in vivo embryonic data, in that the impairments caused by Zinc oxide nanoparticles treatment passed through cell generations; and both gamma-H2AX and NF-kappaB pathways were involved in zinc oxide nanoparticles caused embryo-toxicity...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28389334/loss-of-dusp3-activity-radiosensitizes-human-tumor-cell-lines-via-attenuation-of-dna-repair-pathways
#6
Thompson E P Torres, Lilian C Russo, Alexsandro Santos, Gabriela R Marques, Yuli T Magalhaes, Sartaj Tabassum, Fabio L Forti
BACKGROUND: Radiotherapy causes the regression of many human tumors by increasing DNA damage, and the novel molecular mechanisms underlying the genomic instability leading to cancer progression and metastasis must be elucidated. Atypical dual-specificity phosphatase 3 (DUSP3) has been shown to down-regulate mitogen-activated protein kinases (MAPKs) to control the proliferation and apoptosis of human cancer cells. We have recently identified novel molecular targets of DUSP3 that function in DNA damage response and repair; however, whether DUSP3 affects these processes remains unknown...
April 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28388353/deficiency-in-dna-damage-response-a-new-characteristic-of-cells-infected-with-latent-hiv-1
#7
Dorota Piekna-Przybylska, Gaurav Sharma, Sanjay B Maggirwar, Robert A Bambara
Viruses can interact with host cell molecules responsible for the recognition and repair of DNA lesions, resulting in dysfunctional DNA damage response (DDR). Cells with inefficient DDR are more vulnerable to therapeutic approaches that target DDR, thereby raising DNA damage to a threshold that triggers apoptosis. Here, we demonstrate that 2 Jurkat-derived cell lines with incorporated silent HIV-1 provirus show increases in DDR signaling that responds to formation of double strand DNA breaks (DSBs). We found that phosphorylation of histone H2AX on Ser139 (gamma-H2AX), a biomarker of DSBs, and phosphorylation of ATM at Ser1981, Chk2 at Thr68, and p53 at Ser15, part of signaling pathways associated with DSBs, are elevated in these cells...
May 19, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28351323/gamma-h2ax-can-it-be-established-as-a-classical-cancer-prognostic-factor
#8
REVIEW
Viktoria-Varvara Palla, Georgios Karaolanis, Ioannis Katafigiotis, Ioannis Anastasiou, Paul Patapis, Dimitrios Dimitroulis, Despoina Perrea
Double-strand breaks are among the first procedures taking place in cancer formation and progression as a result of endogenic and exogenic factors. The histone variant H2AX undergoes phosphorylation at serine 139 due to double-strand breaks, and the gamma-H2AX is formatted as a result of genomic instability. The detection of gamma-H2AX can potentially serve as a biomarker for transformation of normal tissue to premalignant and consequently to malignant tissues. gamma-H2AX has already been investigated in a variety of cancer types, including breast, lung, colon, cervix, and ovary cancers...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28098348/impact-of-lysosomal-storage-disorders-on-biology-of-mesenchymal-stem-cells-evidences-from-in-vitro-silencing-of-glucocerebrosidase-gba-and-alpha-galactosidase-a-gla-enzymes
#9
Tiziana Squillaro, Antonucci Ivana, Nicola Alessio, Anna Esposito, Marilena Cipollaro, Marina Melone, Gianfranco Peluso, Liborio Stuppia, Umberto Galderisi
Lysosomal storage disorders (LDS) comprise a group of rare multisystemic diseases resulting from inherited gene mutations that impair lysosomal homeostasis. The most common LSDs, Gaucher disease (GD), and Fabry disease (FD) are caused by deficiencies in the lysosomal glucocerebrosidase (GBA) and alpha-galactosidase A (GLA) enzymes, respectively. Given the systemic nature of enzyme deficiency, we hypothesized that the stem cell compartment of GD and FD patients might be also affected. Among stem cells, mesenchymal stem cells (MSCs) are a commonly investigated population given their role in hematopoiesis and the homeostatic maintenance of many organs and tissues...
January 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28052107/ubiquitin-accumulation-on-disease-associated-protein-aggregates-is-correlated-with-nuclear-ubiquitin-depletion-histone-de-ubiquitination-and-impaired-dna-damage-response
#10
Adi Ben Yehuda, Marwa Risheq, Ofra Novoplansky, Kirill Bersuker, Ron R Kopito, Michal Goldberg, Michael Brandeis
Deposition of ubiquitin conjugates on inclusion bodies composed of protein aggregates is a definitive cytopathological hallmark of neurodegenerative diseases. We show that accumulation of ubiquitin on polyQ IB, associated with Huntington's disease, is correlated with extensive depletion of nuclear ubiquitin and histone de-ubiquitination. Histone ubiquitination plays major roles in chromatin regulation and DNA repair. Accordingly, we observe that cells expressing IB fail to respond to radiomimetic DNA damage, to induce gamma-H2AX phosphorylation and to recruit 53BP1 to damaged foci...
2017: PloS One
https://www.readbyqxmd.com/read/28034704/antioxidants-taken-orally-prior-to-diagnostic-radiation-exposure-can-prevent-dna-injury
#11
Nivethan Velauthapillai, Joe Barfett, Hussein Jaffer, David Mikulis, Kieran Murphy
PURPOSE: To evaluate efficacy of oral antioxidant treatment given to patients before radiologic procedures in reducing x-ray-induced DNA damage. MATERIALS AND METHODS: In a single-center prospective controlled trial, antioxidant treatment with 2 g ascorbate, 1.2 g N-acetylcysteine, 600 mg lipoic acid, and 30 mg beta carotene was given to 5 consecutive participants before undergoing clinically indicated technetium-99m methylene diphosphonate ((99m)Tc MDP) bone scans for cancer staging...
March 2017: Journal of Vascular and Interventional Radiology: JVIR
https://www.readbyqxmd.com/read/27814570/chromosomal-aberrations-clastogens-vs-aneugens
#12
Masayuki Mishima
Current anticancer therapy may be one of the most important exogenous sources of exposure to genotoxic agents in US, Japan, and Europe, where approximately 40-55 percent of the population is diagnosed with cancer at a certain point in their life. This review focuses on recent efforts to integrate a novel biomarker, gamma-H2AX, into anticancer drug screening to classify the mode of action (MoA) for genotoxic outcome into clastogenicity and aneugenicity, a distinction that has considerable impact on risk assessment and control strategy...
January 1, 2017: Frontiers in Bioscience (Scholar Edition)
https://www.readbyqxmd.com/read/27779695/enhancement-of-radiosensitivity-by-inhibition-of-c-jun-n-terminal-kinase-activity-in-a-lewis-lung-carcinoma%C3%A2-bearing-subcutaneous-tumor-mouse-model
#13
Chun-Hao Li, Sa-Hoe Lim, Hyang-Hwa Ryu, Kyung-Sub Moon, Tae-Young Jung, Shin Jung
Stereotactic radiosurgery has been recognized as an effective treatment approach for metastatic brain tumors. By increasing the sensitivity of the tumor to radiation and decreasing the marginal dose, it is possible to improve therapeutic efficacy and decrease side-effects. In radiation-induced cells, c-Jun N-terminal kinase (JNK) signaling mediates the phosphorylation of H2AX, which indicates DNA damage sensitivity and modulates the effect of radiation. Lewis lung cancer (LLC) and breast cancer (4T1) cells were irradiated with a Gamma Knife in cell culture tubes...
December 2016: Oncology Reports
https://www.readbyqxmd.com/read/27778526/the-reneb-operational-basis-complement-of-established-biodosimetric-assays
#14
Andrzej Wojcik, Ursula Oestreicher, Lleonard Barrios, Anne Vral, Georgia Terzoudi, Elizabeth Ainsbury, Kai Rothkamm, Francois Trompier, Ulrike Kulka
PURPOSE: To set up an operational basis of the Realizing the European Network of Biodosimetry (RENEB) network within which the application of seven established biodosimetric tools (the dicentric assay, the FISH assay, the micronucleus assay, the PCC assay, the gamma-H2AX assay, electron paramagnetic resonance and optically stimulated luminescence) will be compared and standardized among the participating laboratories. METHODOLOGY: Two intercomparisons were organized where blood samples and smartphone components were irradiated, coded and sent out to participating laboratories for dosimetric analysis...
January 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/27686532/gamma-h2ax-upregulation-caused-by-wip1-deficiency-increases-depression-related-cellular-senescence-in-hippocampus
#15
Zhi-Yong He, Wen-Yue Wang, Wei-Yan Hu, Lu Yang, Yan Li, Wei-Yuan Zhang, Ya-Shu Yang, Si-Cheng Liu, Feng-Lan Zhang, Rong Mei, Da Xing, Zhi-Cheng Xiao, Ming Zhang
The PP2C family member Wild-type p53-induced phosphatase 1 (Wip1) critically regulates DNA damage response (DDR) under stressful situations. In the present study, we investigated whether Wip1 expression was involved in the regulation of DDR-induced and depression-related cellular senescence in mouse hippocampus. We found that Wip1 gene knockout (KO) mice showed aberrant elevation of hippocampal cellular senescence and of γ-H2AX activity, which is known as a biomarker of DDR and cellular senescence, indicating that the lack of Wip1-mediated γ-H2AX dephosphorylation facilitates cellular senescence in hippocampus...
September 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27686523/the-second-gamma-h2ax-assay-inter-comparison-exercise-carried-out-in-the-framework-of-the-european-biodosimetry-network-reneb
#16
COMPARATIVE STUDY
Jayne Moquet, Stephen Barnard, Albena Staynova, Carita Lindholm, Octávia Monteiro Gil, Vanda Martins, Ute Rößler, Anne Vral, Charlot Vandevoorde, Maria Wojewódzka, Kai Rothkamm
PURPOSE: Within the EU RENEB project, seven laboratories have taken part in training and harmonisation activities to strengthen triage gamma-H2AX-based radiation exposure assessment. This has culminated in a second triage biodosimetry exercise. MATERIALS AND METHODS: Whole blood and separated lymphocyte samples were homogenously irradiated with (60)Co gamma rays at 0.5, 2.5 (blind samples), 0 and 2 Gy (reference samples). Following post-exposure incubations of 4 and 24 h, 16 samples were shipped on ice packs to each partner...
January 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/27551505/induction-and-inhibition-of-the-pan-nuclear-gamma-h2ax-response-in-resting-human-peripheral-blood-lymphocytes-after-x-ray-irradiation
#17
D Ding, Y Zhang, J Wang, X Zhang, Y Gao, L Yin, Q Li, J Li, H Chen
Human peripheral blood lymphocytes (HPBLs) are one of the most sensitive cells to ionizing radiation (IR) in the human body, and IR-induced DNA damage and functional impairment of HPBLs are the adverse consequences of IR accidents and major side effects of radiotherapy. Phosphorylated H2AX (γH2AX) is a sensitive marker for DNA double-strand breaks, but the role and regulation of the pan-nuclear γH2AX response in HPBLs after IR remain unclear. We herein demonstrated that the pan-nuclear γH2AX signals were increased in a time- and dose-dependent manner, colocalized with >94% of TUNEL apoptotic staining, and displayed a typical apoptotic pattern in resting HPBLs after low LET X-ray IR...
2016: Cell Death Discovery
https://www.readbyqxmd.com/read/27500188/telomere-dysfunction-induced-foci-tif-analysis
#18
Ilgen Mender, Jerry W Shay
Telomerase maintains telomeric DNA in eukaryotes during early developments, ~90% of cancer cells and some proliferative stem like cells. Telomeric repeats at the end of chromosomes are associated with the shelterin complex. This complex consists of TRF1, TRF2, Rap1, TIN2, TPP1, POT1 which protect DNA from being recognized as DNA double-stranded breaks. Critically short telomeres or impaired shelterin proteins can cause telomere dysfunction, which eventually induces DNA damage responses at the telomeres. DNA damage responses can be identified by antibodies to 53BP1, gammaH2AX, Rad17, ATM, and Mre11...
November 20, 2015: Bio-protocol
https://www.readbyqxmd.com/read/27475622/a-practical-alpha-particle-irradiator-for-studying-internal-alpha-particle-exposure
#19
Ki-Man Lee, Ui-Seob Lee, Eun-Hee Kim
An alpha particle irradiator has been built in the Radiation Bioengineering Laboratory at Seoul National University (SNU) to investigate the cellular responses to alpha emissions from radon and the progeny. This irradiator is designed to have the energy of alpha particles entering target cells similar to that of alpha emissions from the radon progeny Po-218 and Po-214 residing in the human respiratory tract. For the SNU alpha particle irradiator, an irradiation system is equipped with cell dishes of 4µm thick Mylar bottom and a special setup of cells on slide for gamma-H2AX assay...
September 2016: Applied Radiation and Isotopes
https://www.readbyqxmd.com/read/27465136/effects-of-aging-and-oxidative-stress-on-spermatozoa-of-superoxide-dismutase-1-and-catalase-null-mice
#20
Johanna S Selvaratnam, Bernard Robaire
Advanced paternal age is linked to complications in pregnancy and genetic diseases in offspring. Aging results in excess reactive oxygen species (ROS) and DNA damage in spermatozoa; this damage can be transmitted to progeny with detrimental consequences. Although there is a loss of antioxidants with aging, the impact on aging male germ cells of the complete absence of either catalase (CAT) or superoxide dismutase 1 (SOD1) has not been investigated. We used CAT-null (Cat(-/-)) and SOD1-null (Sod(-/-)) mice to determine whether loss of these antioxidants increases germ cell susceptibility to redox dysfunction with aging...
September 2016: Biology of Reproduction
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