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h2ax and irradiation

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https://www.readbyqxmd.com/read/29155797/immunofluorescence-microscopy-of-%C3%AE-h2ax-and-53bp1-for-analyzing-the-formation-and-repair-of-dna-double-strand-breaks
#1
Henning D Popp, Susanne Brendel, Wolf-Karsten Hofmann, Alice Fabarius
DNA double-strand breaks (DSB) are serious DNA lesions. Analysis of the formation and repair of DSB is relevant in a broad spectrum of research areas including genome integrity, genotoxicity, radiation biology, aging, cancer, and drug development. In response to DSB, the histone H2AX is phosphorylated at Serine 139 in a region of several megabase pairs forming discrete nuclear foci detectable by immunofluorescence microscopy. In addition, 53BP1 (p53 binding protein 1) is another important DSB-responsive protein promoting repair of DSB by nonhomologous end-joining while preventing homologous recombination...
November 3, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29141658/thioredoxin-mitigates-radiation-induced-hematopoietic-stem-cell-injury-in-mice
#2
Pasupathi Sundaramoorthy, Qinhong Wang, Zhihong Zheng, Yiqun Jiao, Benny J Chen, Phuong L Doan, Nelson J Chao, Yubin Kang
BACKGROUND: Radiation exposure poses a significant threat to public health. Hematopoietic injury is one of the major manifestations of acute radiation sickness. Protection and/or mitigation of hematopoietic stem cells (HSCs) from radiation injury is an important goal in the development of medical countermeasure agents (MCM). We recently identified thioredoxin (TXN) as a novel molecule that has marked protective and proliferative effects on HSCs. In the current study, we investigated the effectiveness of TXN in rescuing mice from a lethal dose of total body radiation (TBI) and in enhancing hematopoietic reconstitution following a lethal dose of irradiation...
November 15, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29128690/transcriptome-based-biological-dosimetry-of-gamma-radiation-in-arabidopsis-using-dna-damage-response-genes
#3
Tae Ho Ryu, Jin Kyu Kim, Jeong-Il Kim, Jin-Hong Kim
Plants are used as representative reference biota for the biological assessment of environmental risks such as ionizing radiation due to their immobility. This study proposed a faster, more economical, and more effective method than conventional cytogenetic methods for the biological dosimetry of ionizing radiation in plants (phytodosimetry). We compared various dose-response curves for the radiation-induced DNA damage response (DDR) in Arabidopsis thaliana after relatively "low-dose" gamma irradiation (3, 6, 12, 24, and 48 Gy) below tens of Gy using comet (or single-cell gel electrophoresis), gamma-H2AX, and transcriptomic assays of seven DDR genes (AGO2, BRCA1, GRG, PARP1, RAD17, RAD51, and RPA1E) using quantitative real time PCR...
November 9, 2017: Journal of Environmental Radioactivity
https://www.readbyqxmd.com/read/29099268/atm-mediated-mitochondrial-damage-response-triggered-by-nuclear-dna-damage-in-normal-human-lung-fibroblasts
#4
Tsutomu Shimura, Megumi Sasatani, Hidehiko Kawai, Kenji Kamiya, Junya Kobayashi, Kenshi Komatsu, Naoki Kunugita
Ionizing radiation (IR) elevates mitochondrial oxidative phosphorylation (OXPHOS) in response to the energy requirement for DNA damage responses. Reactive oxygen species (ROS) released during mitochondrial OXPHOS may cause oxidative damage to mitochondria in irradiated cells. In this paper, we investigated the association between nuclear DNA damage and mitochondrial damage following IR in normal human lung fibroblasts. In contrast to low-doses of acute single radiation, continuous exposure of chronic radiation or long-term exposure of fractionated radiation (FR) induced persistent Rad51 and γ-H2AX foci at least 24 hours after IR in irradiated cells...
November 3, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29089078/-nlrp3-inflammasome-induces-pyroptosis-in-lung-tissues-of-radiation-induced-lung-injury-in-mice
#5
Rong Han, Dongming Wu, Shihua Deng, Teng Liu, Ting Zhang, Ying Xu
Objective To establish a radiation-induced lung injury model and investigate the role of caspase-1-dependent programmed cell death (pyroptosis) in the pathogenesis of radiation pneumonitis. Methods BALB/c mice were sacrificed after receiving 5-day 15 Gy X-ray irradiation at chest cavity. The pathological changes of pulmonary tissues were observed by HE staining. The apoptosis of lung tissues cells after irradiation was detected by TUNEL assay. The expressions of γ-H2AX, ki67, NLR family pyrin domain containing 3 (NLRP3), caspase-1, apoptosis-associated speck-like protein containing a CARD (ASC/TMS-1) were detected by Western blot analysis...
September 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/29054934/radiation-induced-dna-damage-in-operators-performing-endovascular-aortic-repair
#6
Tamer El-Sayed, Ashish S Patel, Jun S Cho, James A Kelly, Francesca E Ludwinski, Prakash Saha, Oliver T Lyons, Alberto Smith, Bijan Modarai
Background -Radiation exposure during fluoroscopically-guided interventions such as endovascular aortic repair (EVAR) is a growing concern for operators. This study aimed to measure DNA damage/repair markers in operators perfoming EVAR. Methods -Expression of the DNA damage/repair marker, gamma-H2AX (γ-H2AX) and DNA damage response (DDR) marker, phosphorylated ataxia telangiectasia mutated (pATM), were quantified in circulating lymphocytes in operators during the peri-operative period of endovascular (infra-renal [IEVAR], branched [BEVAR] and fenestrated [FEVAR]) and open aortic repair using flow cytometry...
October 20, 2017: Circulation
https://www.readbyqxmd.com/read/29053406/super-resolution-nanoscopy-imaging-applied-to-dna-double-strand-breaks
#7
Sofia D'Abrantes, Sarah Gratton, Pamela Reynolds, Verena Kriechbaumer, Joseph McKenna, Stephen Barnard, Dave Clarke, Stanley W Botchway
Genomic deoxyribonucleic acid (DNA) is continuously being damaged by endogenous processes such as metabolism or by exogenous events such as radiation. The specific phosphorylation of histone H2AX on serine residue 139, described as γ-H2AX, is an excellent indicator or marker of DNA double-strand breaks (DSBs). The yield of γ-H2AX (foci) is shown to have some correlation with the dose of radiation or other DSB-causing agents. However, there is some discrepancy in the DNA DSB foci yield among imaging and other methods such as gel electrophoresis...
October 20, 2017: Radiation Research
https://www.readbyqxmd.com/read/29042418/socs1-gene-therapy-improves-radiosensitivity-and-enhances-irradiation-induced-dna-damage-in-esophageal-squamous-cell-carcinoma
#8
Takahito Sugase, Tsuyoshi Takahashi, Satoshi Serada, Minoru Fujimoto, Kosuke Hiramatsu, Tomoharu Ohkawara, Koji Tanaka, Yasuhiro Miyazaki, Tomoki Makino, Yukinori Kurokawa, Makoto Yamasaki, Kiyokazu Nakajima, Tadamitsu Kishimoto, Masaki Mori, Yuichiro Doki, Tetsuji Naka
STAT3 has been implicated recently in radioresistance in cancer. In this study, we investigated the association between STAT3 and radioresistance in esophageal squamous cell carcinoma (ESCC). Strong expression of activated phospho-STAT3 (p-STAT3) was observed in 16/22 ESCC patients with preoperative chemoradiotherapy (CRT), compared to 9/24 patients with surgery alone, where the prognosis of those with CRT was poor. Expression of p-STAT3 and the anti-apoptotic proteins Mcl-1 and survivin was strongly induced in ESCC cells by irradiation...
October 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/29034758/feasibility-study-on-the-use-of-gold-nanoparticles-in-fractionated-kilovoltage-x-ray-treatment-of-melanoma
#9
So-Ra Kim, Eun-Hee Kim
PURPOSE: Despite the high radioresistance of melanoma, unresectable lesions can be subjected to radiation treatment with the use of gold nanoparticles (AuNPs) as a dose-enhancing agent preferentially loaded on these lesions. The modality of single high-dose treatment has been investigated to confirm its therapeutic efficiency for AuNP-treated melanoma cells. This study explores the feasibility of utilizing AuNPs in fractionated radiation therapy of melanoma for further therapeutic gain...
October 16, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28991227/essential-role-of-mettl3-mediated-m-6-a-modification-in-glioma-stem-like-cells-maintenance-and-radioresistance
#10
A Visvanathan, V Patil, A Arora, A S Hegde, A Arivazhagan, V Santosh, K Somasundaram
Despite advances in biology and therapeutic modalities, existence of highly tumorigenic glioma stem-like cells (GSCs) makes glioblastomas (GBMs) invincible. N6-methyl adenosine (m(6)A), one of the abundant mRNA modifications catalyzed by methyltransferase-like 3 and 14 (METTL3/14), influences various events in RNA metabolism. Here, we report the crucial role of METTL3-mediated m(6)A modification in GSC (neurosphere) maintenance and dedifferentiation of glioma cells. METTL3 expression is elevated in GSC and attenuated during differentiation...
October 9, 2017: Oncogene
https://www.readbyqxmd.com/read/28985197/downregulation-of-lncrna-x-inactive-specific-transcript-xist-suppresses-cell-proliferation-and-enhances-radiosensitivity-by-upregulating-mir-29c-in-nasopharyngeal-carcinoma-cells
#11
Qian Han, Liang Li, Hengpo Liang, Yaqiong Li, Jiacun Xie, Zhibin Wang
BACKGROUND LncRNA X inactive specific transcript (XIST) was reported to function as an oncogene in nasopharyngeal carcinoma cells (NPC) by sponging miR-34a-5p. However, the role of XIST in modulating the radiosensitivity of NPC cells and its mechanism still remain undefined. MATERIAL AND METHODS The expressions of XIST and miR-29c in NPC cells were evaluated by qRT-PCR. CNE1 and CNE2 cells were transfected with si-XIST, pcDNA-XIST, miR-29c mimics, anti-miR-29c, or respective controls by Lipofectamine 2000. The effects of XIST knockdown and miR-29c overexpression on cell proliferation, survival fraction, and γ-H2AX expression were investigated by CCK-8 assay, colony formation assay, immunofluorescence, and Western blot, respectively...
October 6, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28973009/tlr9-stimulation-of-b-cells-induces-transcription-of-p53-and-prevents-spontaneous-and-irradiation-induced-cell-death-independent-of-dna-damage-responses-implications-for-common-variable-immunodeficiency
#12
Kristine Lillebø Holm, Randi Gussgard Syljuåsen, Grete Hasvold, Lene Alsøe, Hilde Nilsen, Kristina Ivanauskiene, Philippe Collas, Sergey Shaposhnikov, Andrew Collins, Randi Larsen Indrevær, Pål Aukrust, Børre Fevang, Heidi Kiil Blomhoff
In the present study, we address the important issue of whether B-cells protected from irradiation-induced cell death, may survive with elevated levels of DNA damage. If so, such cells would be at higher risk of gaining mutations and undergoing malignant transformation. We show that stimulation of B-cells with the TLR9 ligands CpG-oligodeoxynucleotides (CpG-ODN) prevents spontaneous and irradiation-induced death of normal peripheral blood B-cells, and of B-cells from patients diagnosed with Common variable immunodeficiency (CVID)...
2017: PloS One
https://www.readbyqxmd.com/read/28915641/reevaluation-of-atr-signaling-in-primary-resting-chronic-lymphocytic-leukemia-cells-evidence-for-pro-survival-or-pro-apoptotic-function
#13
Maxime Beyaert, Eliza Starczewska, Ana Cristina González Pérez, Nicolas Vanlangendonck, Pascale Saussoy, Gaëlle Tilman, Anne De Leener, Marie-Christiane Vekemans, Eric Van Den Neste, Françoise Bontemps
ATM, primarily activated by DNA double-strand breaks, and ATR, activated by single-stranded DNA, are master regulators of the cellular response to DNA damage. In primary chronic lymphocytic leukemia (CLL) cells, ATR signaling is considered to be switched off due to ATR downregulation. Here, we hypothesized that ATR, though expressed at low protein level, could play a role in primary resting CLL cells after genotoxic stress. By investigating the response of CLL cells to UV-C irradiation, a prototypical activator of ATR, we could detect phosphorylation of ATR at Thr-1989, a marker for ATR activation, and also observed that selective ATR inhibitors markedly decreased UV-C-induced phosphorylation of ATR targets, including H2AX and p53...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28902347/measuring-the-response-of-human-head-and-neck-squamous-cell-carcinoma-to-irradiation-in-a-microfluidic-model-allowing-customized-therapy
#14
Ramsah Cheah, Rishi Srivastava, Nicholas D Stafford, Andrew W Beavis, Victoria Green, John Greenman
Radiotherapy is the standard treatment for head and neck squamous cell carcinoma (HNSCC), however, radioresistance remains a major clinical problem despite significant improvements in treatment protocols. Therapeutic outcome could potentially be improved if a patient's tumour response to irradiation could be predicted ex vivo before clinical application. The present study employed a bespoke microfluidic device to maintain HNSCC tissue whilst subjecting it to external beam irradiation and measured the responses using a panel of cell death and proliferation markers...
October 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28887524/selective-uptake-of-epidermal-growth-factor-conjugated-gold-nanoparticle-egf-gnp-facilitates-non-thermal-plasma-ntp-mediated-cell-death
#15
Wanil Kim, Kyung-Yoon Na, Kyung-Ha Lee, Hyun Wook Lee, Jae Koo Lee, Kyong-Tai Kim
Non-thermal atmospheric pressure plasma (NTP) has been shown to induce cell death in various mammalian cancer cells. Accumulated evidence also shows that NTP could be clinically used in cancer therapy. However, the current NTP-based applications lack target specificity. Here, a novel method in NTP-mediated cancer therapeutics was described with enhanced target specificity by treating EGF (epidermal growth factor)-conjugated GNP (gold nanoparticle). The treatment with EGF-conjugated GNP complex, followed by NTP irradiation showed selective apoptosis of cells having receptor-mediated endocytosis...
September 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28852434/a-new-natural-antioxidant-mixture-protects-against-oxidative-and-dna-damage-in-endothelial-cell-exposed-to-low-dose-irradiation
#16
T Cervelli, D Panetta, T Navarra, S Gadhiri, P Salvadori, A Galli, D Caramella, G Basta, E Picano, S Del Turco
Exposure to ionizing radiation during diagnostic procedures increases systemic oxidative stress and predisposes to higher risk of cancer and cardiovascular disease development. Many studies indicated that antioxidants protect against radiation-induced damage and have high efficacy and lack of toxicity in preventing radiation exposure damages. The purpose of this study was to investigate the in vitro protective effect of a new antioxidant mixture, named RiduROS, on oxidative stress generation and DNA double-strand breaks (DSBs) induced by low doses of X-rays in endothelial cells...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28829673/oxygen-enhancement-ratio-in-radiation-induced-initial-dsbs-by-an-optimized-flow-cytometry-based-gamma-h2ax-analysis-in-a549-human-cancer-cells
#17
Shigeaki Sunada, Hirokazu Hirakawa, Akira Fujimori, Mitsuru Uesaka, Ryuichi Okayasu
High-linear energy transfer (LET) heavy ions cause higher therapeutic effects than low-LET radiation due to lower dependency on oxygen concentration in tumor cell killing. The lethality after irradiation largely depends on DNA double-strand breaks (DSBs), however the detailed LET dependency for DSB induction under oxic and hypoxic conditions has not been reported. Therefore, we evaluated the oxygen enhancement ratio (OER) of heavy ion-induced DSB induction using a highly-optimized flow cytometry-based method of γ-H2AX detection...
November 2017: Radiation Research
https://www.readbyqxmd.com/read/28797171/novel-composite-drug-delivery-system-as-a-novel-radio-sensitizer-for-the-local-treatment-of-cervical-carcinoma
#18
Shan Xu, Yu Ying Tang, Yan Xin Yu, Qin Yun, Jing Pin Yang, Heng Zhang, Qiuxia Peng, Xiaoyang Sun, Ling Lin Yang, ShaoZhi Fu, Jing Bo Wu
In this study, we investigated in vivo radiosensitizing effects of a gel-based dual drug delivery system (DDS) (PECE/DDP + mPEG-PCL/PTX, or PDMP) in a cervical cancer model, and determined its possible mechanisms of action. A xenograft cervical cancer model was used to investigate the radio sensitization effect of PDMP. Mice underwent paclitaxel (PTX) + cisplatin (DDP), PECE, or PDMP treatment followed by single radiation doses ranging from 0 Gy to 20 Gy. Radio sensitization was analyzed by tumor regrowth delay (TGD)...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28794020/adenovirus-core-protein-vii-down-regulates-the-dna-damage-response-on-the-host-genome
#19
Daphne C Avgousti, Ashley N Della Fera, Clayton J Otter, Christin Herrmann, Neha J Pancholi, Matthew D Weitzman
Viral manipulation of cellular proteins allows viruses to suppress host defenses and generate infectious progeny. Due to the linear double-stranded DNA nature of the adenovirus genome, the cellular DNA damage response (DDR) is considered a barrier for successful infection. The adenovirus genome is packaged with protein VII, a viral-encoded histone-like core protein that is suggested to protect incoming viral genomes from detection by cellular DNA damage machinery. We showed that protein VII localizes to host chromatin during infection, leading us to hypothesize that protein VII may affect DNA damage responses on the cellular genome...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28766757/sesamol-ameliorates-radiation-induced-dna-damage-in-hematopoietic-system-of-whole-body-%C3%AE-irradiated-mice
#20
Arun Kumar, Sandeep Choudhary, Jawahar S Adhikari, Nabo K Chaudhury
Ionizing radiation exposure is harmful and at high doses can lead to acute hematopoietic radiation syndrome. Therefore, agents that can protect hematopoietic system are important for development of radioprotector. Sesamol is a potential molecule for development of radioprotector due to its strong free radical scavenging and antioxidant properties. In the present study, sesamol was evaluated for its role in DNA damage and repair in hematopoietic system of γ-irradiated CB57BL/6 mice and compared with amifostine...
August 2, 2017: Environmental and Molecular Mutagenesis
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