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Radiation effects on dna

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https://www.readbyqxmd.com/read/29163581/identification-of-substitutions-and-small-insertion-deletions-induced-by-carbon-ion-beam-irradiation-in-arabidopsis-thaliana
#1
Yan Du, Shanwei Luo, Xin Li, Jiangyan Yang, Tao Cui, Wenjian Li, Lixia Yu, Hui Feng, Yuze Chen, Jinhu Mu, Xia Chen, Qingyao Shu, Tao Guo, Wenlong Luo, Libin Zhou
Heavy-ion beam irradiation is one of the principal methods used to create mutants in plants. Research on mutagenic effects and molecular mechanisms of radiation is an important subject that is multi-disciplinary. Here, we re-sequenced 11 mutagenesis progeny (M3) Arabidopsis thaliana lines derived from carbon-ion beam (CIB) irradiation, and subsequently focused on substitutions and small insertion-deletion (INDELs). We found that CIB induced more substitutions (320) than INDELs (124). Meanwhile, the single base INDELs were more prevalent than those in large size (≥2 bp)...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29161272/global-transcriptome-profile-reveals-abundance-of-dna-damage-response-and-repair-genes-in-individuals-from-high-level-natural-radiation-areas-of-kerala-coast
#2
Vinay Jain, Birajalaxmi Das
The high level natural radiation areas (HLNRA) of Kerala coast in south west India is unique for its wide variation in the background radiation dose (<1.0mGy to 45mGy/year) and vast population size. Several biological studies conducted in this area did not reveal any adverse effects of chronic low dose and low dose rate radiation on human population. In the present study, global transcriptome analysis was carried out in peripheral blood mono-nuclear cells of 36 individuals belonging to different background dose groups [NLNRA, (Group I, ≤1...
2017: PloS One
https://www.readbyqxmd.com/read/29157749/mithramycin-a-enhances-tumor-sensitivity-to-mitotic-catastrophe-resulting-from-dna-damage
#3
Bradley T Scroggins, Jeffrey Burkeen, Ayla O White, Eun Joo Chung, Darmood Wei, Su I Chung, Luca F Valle, Shilpa S Patil, Grace McKay-Corkum, Kathryn E Hudak, W Marston Linehan, Deborah E Citrin
PURPOSE: Specificity protein 1 (SP1) is involved in the transcription of several genes implicated in tumor maintenance. We investigated the effects of mithramycin A (MTA), an inhibitor of SP1 DNA binding, on radiation response. METHODS AND MATERIALS: Clonogenic survival after irradiation was assessed in 2 tumor cell lines (A549, UM-UC-3) and 1 human fibroblast line (BJ) after SP1 knockdown or MTA treatment. DNA damage repair was evaluated using γH2AX foci formation, and mitotic catastrophe was assessed using nuclear morphology...
October 12, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29157079/zeb1-inhibition-sensitizes-cells-to-the-atr-inhibitor-ve-821-by-abrogating-epithelial-mesenchymal-transition-and-enhancing-dna-damage
#4
Na Song, Wei Jing, Ce Li, Ming Bai, Yu Cheng, Heming Li, Kezuo Hou, Yanrong Li, Kai Wang, Zhi Li, Yunpeng Liu, Xiujuan Qu, Xiaofang Che
The ataxia-telangiectasia-mutated (ATM) and rad3-related (ATR) checkpoint pathway plays an essential role in modulating cellular responses to replication stress and DNA damage to maintain genomic stability. In various tumors, cancer cells have increased dependence on ATR signaling for survival, making ATR a promising target for cancer therapy. ATR inhibitors sensitize multiple tumor cell types to radiation and DNA-damaging agents, but application of an ATR inhibitor alone shows limited efficacy. In the present study, we investigated the role of epithelial-to-mesenchymal transition (EMT) and the EMT transcription factor ZEB1 in regulating cell sensitivity to the ATR inhibitor VE-821...
November 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29157078/evolving-paradigms-for-the-biological-response-to-low-dose-ionising-radiation-the-role-of-epigenetics
#5
Paul N Schofield, Monika Kondratowicz
PURPOSE: In the late 1990s it had become clear that the long-standing paradigm for the action of radiation on living cells and organisms did not have sufficient power to explain the observed effects of low dose ionising radiation. The purpose of this commentary is to examine the experiments that lead up to the modification of the classic paradigm consequent on these observations, their historical precedents, and the development of our understanding of the role of epigenetics in low dose radiation effects...
November 20, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/29156909/genetic-biomarkers-associated-with-response-to-palliative-radiotherapy-in-patients-with-painful-bone-metastases
#6
Anthony Furfari, Bo Angela Wan, Keyue Ding, Andrew Wong, Liting Zhu, Andrea Bezjak, Rebecca Wong, Carolyn F Wilson, Carlo DeAngelis, Azar Azad, Edward Chow, George S Charames
BACKGROUND: Palliative radiotherapy (RT) is effective in patients with painful bone metastases. Genetic factors may identify subgroup of patients who responded to RT. To identify DNA biomarkers associated with response to palliative RT. METHODS: Patients who received a single 8 Gy dose of RT for painful bone metastases were categorised into responders (n=36), non-responders (NR) (n=71). Saliva samples were sequenced to identify single-nucleotide variants (SNVs) in genes with known disease-causing variants from inflammation, radiation response, and DNA damage pathways...
October 10, 2017: Annals of Palliative Medicine
https://www.readbyqxmd.com/read/29156644/akt1-stimulates-homologous-recombination-repair-of-dna-double-strand-breaks-in-a-rad51-dependent-manner
#7
Katharina Mueck, Simone Rebholz, Mozhgan Dehghan Harati, H Peter Rodemann, Mahmoud Toulany
Akt1 is known to promote non-homologous end-joining (NHEJ)-mediated DNA double-strand break (DSB) repair by stimulation of DNA-PKcs. In the present study, we investigated the effect of Akt1 on homologous recombination (HR)-dependent repair of radiation-induced DSBs in non-small cell lung cancer (NSCLC) cells A549 and H460. Akt1-knockdown (Akt1-KD) significantly reduced Rad51 protein level, Rad51 foci formation and its colocalization with γH2AX foci after irradiation. Moreover, Akt1-KD decreased clonogenicity after treatment with Mitomycin C and HR repair, as tested by an HR-reporter assay...
November 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29155723/one-step-protocol-for-evaluation-of-the-mode-of-radiation-induced-clonogenic-cell-death-by-fluorescence-microscopy
#8
Daijiro Kobayashi, Atsushi Shibata, Takahiro Oike, Takashi Nakano
Research on ionizing radiation (IR)-induced clonogenic cell death is important for understanding the effect of IR on malignant tumors and normal tissues. Here, we describe a quick and cost-effective one-step assay for simultaneously assessing the major modes of clonogenic cell death induced by IR, i.e., apoptosis, mitotic catastrophe, and cellular senescence. In this method, cells grown on a cover slip are irradiated with X-rays and stained with 4',6-diamidino-2-phenylindole dihydrochloride (DAPI). Using fluorescence microscopy, apoptosis, mitotic catastrophe, and cellular senescence are identified based on the characteristic morphologies of the DAPI-stained nuclei...
October 23, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29152122/cisplatin-radiosensitizes-radioresistant-human-mesenchymal-stem-cells
#9
Alexander Rühle, Ramon Lopez Perez, Christin Glowa, Klaus-Josef Weber, Anthony D Ho, Jürgen Debus, Rainer Saffrich, Peter E Huber, Nils H Nicolay
Cisplatin-based chemo-radiotherapy is widely used to treat cancers with often severe therapy-associated late toxicities. While mesenchymal stem cells (MSCs) were shown to aid regeneration of cisplatin- or radiation-induced tissue lesions, the effect of the combined treatment on the stem cells remains unknown. Here we demonstrate that cisplatin treatment radiosensitized human bone marrow-derived MSCs in a dose-dependent manner and increased levels of radiation-induced apoptosis. However, the defining stem cell properties of MSCs remained largely intact after cisplatin-based chemo-radiation, and stem cell motility, adhesion, surface marker expression and the characteristic differentiation potential were not significantly influenced...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29152107/neoadjuvant-olaparib-targets-hypoxia-to-improve-radioresponse-in-a-homologous-recombination-proficient-breast-cancer-model
#10
Gerben R Borst, Ramya Kumareswaran, Hatice Yücel, Seyda Telli, Trevor Do, Trevor McKee, Gaetano Zafarana, Jos Jonkers, Marcel Verheij, Mark J O'Connor, Sven Rottenberg, Robert G Bristow
Clinical trials are studying the benefits of combining the PARP-1 inhibitor olaparib with chemotherapy and radiotherapy treatment in a variety of cancer increasing the therapeutic ratio for olaparib may come from its ability to modify the tumour microenvironment by targeting homologous recombination-deficient, hypoxic tumour clonogens, and/or increasing tumour-associated vasodilation to improve oxygenation. Herein, we investigated the effect of prolonged neoadjuvant exposure to olaparib on the tumor microenvironment using a genetically-engineered mouse p53-/- syngeneic breast cancer model, which is proficient in homology-directed DNA repair...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29150967/drug-delivery-strategies-for-chemoprevention-of-uvb%C3%A2-induced-skin-cancer-a-review
#11
REVIEW
Arvind Bagde, Arindam Mondal, Mandip Singh
Annually, more skin cancer cases are diagnosed than the collective incidence of the colon, lung, breast and prostate cancer. Persistent contact with sunlight is a primary cause for all the skin malignancies. UVB radiation induces reactive oxygen species (ROS) production in the skin which eventually leads to DNA damage and mutation. Various delivery approaches for the skin cancer treatment/prevention have been evolving and are directed towards improvements in terms of delivery modes, therapeutic agents and site-specificity of therapeutics delivery...
November 18, 2017: Photodermatology, Photoimmunology & Photomedicine
https://www.readbyqxmd.com/read/29148554/modelling-direct-dna-damage-for-gold-nanoparticle-enhanced-proton-therapy
#12
Marios Sotiropoulos, Nicholas T Henthorn, John W Warmenhoven, Ranald I Mackay, Karen J Kirkby, Michael J Merchant
Gold nanoparticles have been proven as potential radiosensitizer when combined with protons. Initially the radiosensitization effect was attributed to the physical interactions of radiation with the gold and the production of secondary electrons that induce DNA damage. However, emerging data challenge this hypothesis, supporting the existence of alternative or supplementary radiosensitization mechanisms. In this work we incorporate a realistic cell model with detailed DNA geometry and a realistic gold nanoparticle biodistribution based on experimental data...
November 17, 2017: Nanoscale
https://www.readbyqxmd.com/read/29143344/down-regulation-of-p16-and-mgmt-promotes-the-anti-proliferative-and-pro-apoptotic-effects-of-5-aza-dc-and-radiation-on-cervical-cancer-cells
#13
Guan-di Chen, De-Ying Qian, Zhi-Gang Li, Ge-Ying Fan, Ke-Li You, Yi-Long Wu
Cervical cancer is one of the most common malignancies of the female reproductive system. Therefore, it is critical to investigate the molecular mechanisms involved in the development and progression of cervical cancer. In this study, we stimulated cervical cancer cells with 5-aza-2'-deoxycytidine (5-Aza-dC) and found that this treatment inhibited cell proliferation and induced apoptosis; additionally, methylation of p16 and O-6-methylguanine-DNA methyltransferase (MGMT) was reversed, although their expression was suppressed...
November 15, 2017: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/29141658/thioredoxin-mitigates-radiation-induced-hematopoietic-stem-cell-injury-in-mice
#14
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/29141157/the-devastating-effect-of-exposure-to-high-irradiation-dose-on-liver-and-the-performance-of-synthesized-nano-hap-in-relieve-the-associated-symptoms-in-rats
#15
Eman Ismail Gheriany, Sameh A Awwad
Ionizing radiation is one of the environmental factors that may contribute to liver dysfunction by a mechanism involving oxidative stress. The present investigation was undertaken to study the possible therapeutic effect of nano-HAp on whole body gamma irradiation induced hepatotoxicity in rats. The study consisted of three groups of 10 rats each. Group 1 (control), whereas group 2 received a single dose of γ-radiation (10Gy). The animals in groups 3 was treated with nano-HAp (100 mg/kg b.w.) once / week for three weeks starting in the next day of γ radiation...
November 15, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/29139544/automatic-detection-of-dna-double-strand-sreaks-after-irradiation-using-an-%C3%AE-h2ax-assay
#16
Tim Hohmann, Jacqueline Kessler, Urszula Grabiec, Matthias Bache, Dyrk Vordermark, Faramarz Dehghani
Radiation therapy belongs to the most common approaches for cancer therapy leading amongst others to DNA damage like double strand breaks (DSB). DSB can be used as a marker for the effect of radiation on cells. For visualization and assessing the extent of DNA damage the γH2AX foci assay is frequently used. The analysis of the γH2AX foci assay remains complicated as the number of γH2AX foci has to be counted. The quantification is mostly done manually, being time consuming and leading to person-dependent variations...
November 15, 2017: Histology and Histopathology
https://www.readbyqxmd.com/read/29137877/immune-analysis-of-radium-223-in-patients-with-metastatic-prostate-cancer
#17
Joseph W Kim, Min Sun Shin, Youna Kang, Insoo Kang, Daniel P Petrylak
BACKGROUND: Radium223 (Ra223) delivers high-energy radiation to osteoblastic metastasis of prostate cancer, resulting in irreparable double-stranded DNA damage. The effects of Ra223 on CD8+ T cell subsets in patients with prostate cancer is unknown. PATIENTS AND METHODS: Fifteen men with metastatic prostate cancer with clinical indication for Ra223 without any autoimmune or immune deficiency conditions were enrolled. Patients received a course of Ra223 50 kBq/kg...
October 24, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29137223/hormone-induced-dna-damage-response-and-repair-mediated-by-cyclin-d1-in-breast-and-prostate-cancer
#18
REVIEW
Gabriele Di Sante, Agnese Di Rocco, Claudia Pupo, Mathew C Casimiro, Richard G Pestell
Cell cycle control proteins govern events that leads to the production of two identical daughter cells. Distinct sequential temporal phases, Gap 1 (G1), Gap 0 (G0), Synthesis (S), Gap 2 (G2) and Mitosis (M) are negotiated through a series of check points during which the favorability of the local cellular environment is assessed, prior to replicating DNA [1]. Cyclin D1 has been characterized as a key regulatory subunit of the holoenzyme that promotes the G1/S-phase transition through phosphorylating the pRB protein...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29130778/lack-of-induced-mutagenesis-in-e-coli-or-human-lymphoblast-cell-line-upon-long-term-sub-culturing-in-medium-from-irradiated-meat
#19
Sachin N Hajare, Jyoti Tripathi, Satyendra Gautam
PURPOSE: Current study was aimed to enhance the confidence of consumers as well as entrepreneurs towards food irradiation program. MATERIALS AND METHODS: In this work, safety of high dose (25 kGy) irradiated meat samples (HDIMS) was ascertained by scoring mutation frequency through a long-term sub-culturing study in Escherichia coli MG1655 cells (ATCC 700926) up to 1500 generations (at 1%), 250 generations (at 5 and 10%) and human lymphoblast thymidine kinase heterozygote (TK6) cell line (ATCC CRL-8015) [at two gene loci, tk(-/+) (thymidine kinase) and hprt(+) (Hypoxanthine Phosphoribosyltransferase)] up to 156 generations using goat meat sample...
November 13, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/29128690/transcriptome-based-biological-dosimetry-of-gamma-radiation-in-arabidopsis-using-dna-damage-response-genes
#20
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
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