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Radiation effects on dna

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https://www.readbyqxmd.com/read/29344644/inactivation-of-dna-pk-by-knockdown-dna-pkcs-or-nu7441-impairs-non-homologous-end-joining-of-radiation-induced-double-strand-break-repair
#1
Jun Dong, Yufeng Ren, Tian Zhang, Zhenyu Wang, Clifton C Ling, Gloria C Li, Fuqiu He, Chengtao Wang, Bixiu Wen
The DNA-dependent protein kinase (DNA-PK) complex plays a pivotal role in non-homologous end-joining (NHEJ) repair. We investigated the mechanism of NU7441, a highly selective DNA-PK inhibitor, in NHEJ-competent mouse embryonic fibroblast (MEF) cells and NHEJ-deficient cells and explored the feasibility of its application in radiosensitizing nasopharyngeal carcinoma (NPC) cells. We generated wild-type and DNA-PKcs-/- MEF cells. Clonogenic survival assays, flow cytometry, and immunoblotting were performed to study the effect of NU7441 on survival, cell cycle, and DNA repair...
January 16, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29339439/idh1-2-mutations-sensitize-acute-myeloid-leukemia-to-parp-inhibition-and-this-is-reversed-by-idh1-2-mutant-inhibitors
#2
Remco J Molenaar, Tomas Radivoyevitch, Yasunobu Nagata, Mohammed Khurshed, Bartlomiej Przychodzen, Hideki Makishima, Mingjiang Xu, Fonnet E Bleeker, Johanna W Wilmink, Hetty Carraway, Sudipto Mukherjee, Mikkael A Sekeres, Cornelis J F Van Noorden, Jaroslaw P Maciejewski
PURPOSE: Somatic mutations in IDH1/2 occur in ~20% of patients with myeloid neoplasms, including acute myeloid leukemia (AML). IDH1/2MUT enzymes produce D-2-hydroxyglutarate (D2HG), which associates with increases in DNA damage and improved responses to chemo/radiotherapy and PARP inhibitors in solid tumor cells. Whether this also holds true for IDH1/2MUT AML is not known. EXPERIMENTAL DESIGN: Well-characterized primary IDH1MUT, IDH2MUT and IDH1/2WT AML cells were analyzed for DNA damage and responses to daunorubicin, ionizing radiation and PARP inhibitors...
January 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29338744/new-insights-in-the-relative-radiobiological-effectiveness-of-proton-irradiation
#3
REVIEW
K Ilicic, S E Combs, T E Schmid
BACKGROUND: Proton radiotherapy is a form of charged particle therapy that is preferentially applied for the treatment of tumors positioned near to critical structures due to their physical characteristics, showing an inverted depth-dose profile. The sparing of normal tissue has additional advantages in the treatment of pediatric patients, in whom the risk of secondary cancers and late morbidity is significantly higher. Up to date, a fixed relative biological effectiveness (RBE) of 1...
January 16, 2018: Radiation Oncology
https://www.readbyqxmd.com/read/29335772/investigation-on-the-correlation-between-energy-deposition-and-clustered-dna-damage-induced-by-low-energy-electrons
#4
Wei Liu, Zhenyu Tan, Liming Zhang, Christophe Champion
This study presents the correlation between energy deposition and clustered DNA damage, based on a Monte Carlo simulation of the spectrum of direct DNA damage induced by low-energy electrons including the dissociative electron attachment. Clustered DNA damage is classified as simple and complex in terms of the combination of single-strand breaks (SSBs) or double-strand breaks (DSBs) and adjacent base damage (BD). The results show that the energy depositions associated with about 90% of total clustered DNA damage are below 150 eV...
January 15, 2018: Radiation and Environmental Biophysics
https://www.readbyqxmd.com/read/29333465/in-vivo-exposure-effects-of-99mtc-methoxyisobutylisonitrile-on-the-fdxr-and-xpa-genes-expression-in-human-peripheral-blood-lymphocytes
#5
Mohammad Taghi Bahreyni-Toossi, Habibeh Vosoughi, Hosein Azimian, Abdul Rahim Rezaei, Mehdi Momennezhad
Objectives: In recent years, the application of radiopharmaceuticals in nuclear medicine has increased substantially. Following the diagnostic procedures performed in nuclear medicine departments, such as myocardial perfusion imaging, patients generally receive considerable doses of radiation. Normally, radiation-induced DNA damages are expected following exposure to a low-dose ionizing radiation. In order to detect molecular changes, high-sensitivity techniques must be utilized. The aim of this study was to assess the effect of a low-dose (below 10 mSv) gamma ray on gene expression using quantitative real-time polymerase chain reaction (qRT-PCR)...
2018: Asia Oceania Journal of Nuclear Medicine & Biology
https://www.readbyqxmd.com/read/29333122/metformin-enhanced-in-vitro-radiosensitivity-associates-with-g2-m-cell-cycle-arrest-and-elevated-adenosine-5-monophosphate-activated-protein-kinase-levels-in-glioblastoma
#6
Sebastian Adeberg, Denise Bernhardt, Semi B Harrabi, Nils H Nicolay, Juliane Hörner-Rieber, Laila König, Michael Repka, Angela Mohr, Amir Abdollahi, Klaus-Josef Weber, Juergen Debus, Stefan Rieken
Background: It is hypothesized that metabolism plays a strong role in cancer cell regulation. We have recently demonstrated improved progression-free survival in patients with glioblastoma who received metformin as an antidiabetic substance during chemoradiation. Although metformin is well-established in clinical use the influence of metformin in glioblastoma is far from being understood especially in combination with other treatment modalities such as radiation and temozolomide. Materials and Methods: In this study, we examined the influence of metformin in combinations with radiation and temozolomide on cell survival (clonogenic survival), cell cycle (routine flow cytometric analysis, FACScan), and phosphorylated Adenosine-5'-monophosphate-activated protein kinase (AMPK) (Phopho-AMPKalpha1 - ELISA) levels in glioblastoma cell lines LN18 and LN229...
December 2017: Radiology and Oncology
https://www.readbyqxmd.com/read/29329222/the-influence-of-egfr-inactivation-on-the-radiation-response-in-high-grade-glioma
#7
Oana Alexandru, Stefana Oana Purcaru, Ligia Gabriela Tataranu, Laura Lucan, Juan Castro, Catalin Folcuţi, Stefan-Alexandru Artene, Cristian Tuţă, Anica Dricu
Lack of effectiveness of radiation therapy may arise from different factors such as radiation induced receptor tyrosine kinase activation and cell repopulation; cell capability to repair radiation induced DNA damage; high grade glioma (HGG) tumous heterogeneity, etc. In this study, we analyzed the potential of targeting epidermal growth factor receptor (EGFR) in inducing radiosensitivity in two human HGG cell lines (11 and 15) that displayed similar growth patterns and expressed the receptor protein at the cell surface...
January 12, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29328411/dna-methylation-enzyme-inhibitor-rg108-suppresses-the-radioresistance-of-esophageal-cancer
#8
Yao Ou, Quan Zhang, Yiting Tang, Zhonghua Lu, Xujing Lu, Xifa Zhou, Changmin Liu
Esophageal cancer (EC) is the eighth most common highly aggressive cancer worldwide. The purpose of this study was to investigate the effect of the DNA methyltransferase inhibitor RG108 on the radiosensitivity of EC cells. MTT and clonogenic assays were performed to assess the effect of RG108 on the proliferation and radiosensitivity of Eca‑109 and TE‑1 human EC cells. The cell cycle progression and alterations in apoptosis were analyzed by flow cytometry. For the in vivo analysis, the Eca‑109 cells were inoculated into nude mice to establish tumors...
January 11, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29327017/a-significant-role-of-non-thermal-equilibrated-electrons-in-the-formation-of-deleterious-complex-dna-damage
#9
Takeshi Kai, Akinari Yokoya, Masatoshi Ukai, Kentaro Fujii, Tomohiro Toigawa, Ritsuko Watanabe
Although most of the radiation damage to genomic DNA could be rendered harmless using repair enzymes in a living cell, a certain fraction of the damage is persistent resulting in serious genetic effects, such as mutation induction. In order to understand the mechanisms of the deleterious DNA damage formation in terms of its earliest physical stage at the radiation track end, dynamics of low energy electrons and their thermalization processes around DNA molecules were investigated using a dynamic Monte Carlo code...
January 12, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29325132/dark-tea-extract-mitigates-hematopoietic-radiation-injury-with-antioxidative-activity
#10
Wei Long, Guanghui Zhang, Yinping Dong, Deguan Li
The hematopoietic system is widely studied in radiation research. Tea has been proved to have antioxidative activity. In the present study, we describe the protective effects of dark tea extract (DTE) on radiation-induced hematopoietic injury. DTE administration significantly enhanced the survival rate of mice after 7.0 and 7.5 Gy total body irradiation (TBI). The results showed that DTE not only markedly increased the numbers and cloning potential of hematopoietic cells, but also decreased DNA damages after mice were exposed to 6...
January 9, 2018: Journal of Radiation Research
https://www.readbyqxmd.com/read/29323251/vitamin-e-inhibits-the-uvai-induction-of-light-and-dark-cyclobutane-pyrimidine-dimers-and-oxidatively-generated-dna-damage-in-keratinocytes
#11
George J Delinasios, Mahsa Karbaschi, Marcus S Cooke, Antony R Young
Solar ultraviolet radiation (UVR)-induced DNA damage has acute, and long-term adverse effects in the skin. This damage arises directly by absorption of UVR, and indirectly via photosensitization reactions. The aim of the present study was to assess the effects of vitamin E on UVAI-induced DNA damage in keratinocytes in vitro. Incubation with vitamin E before UVAI exposure decreased the formation of oxidized purines (with a decrease in intracellular oxidizing species), and cyclobutane pyrimidine dimers (CPD)...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29322505/impact-of-bistrand-abasic-sites-and-proximate-orientation-on-dna-global-structure-and-duplex-energetics
#12
Conceição A Minetti, Jeffrey Y Sun, Daniel P Jacobs, Inkoo Kang, David P Remeta, Kenneth J Breslauer
Bistrand lesions embedded within a single helical turn of tridecameric deoxyoligonucleotide duplexes represent a model system for exploring the impact of clustered lesions that occur in vivo and pose a significant challenge to cellular repair machineries. Such investigations are essential for understanding the forces that dictate lesion-induced mutagenesis, carcinogenesis, and cytotoxicity within a context that mimics local helical perturbations caused by an ionizing radiation event. This study characterizes the structural and energy profiles of DNA duplexes harboring synthetic abasic sites (tetrahydrofuran, F) as models of clustered bistrand abasic (AP) lesions...
January 11, 2018: Biopolymers
https://www.readbyqxmd.com/read/29321089/silencing-of-e3-ubiquitin-ligase-rnf8-enhances-ionizing-radiation-sensitivity-of-5-medulloblastoma-cells-by-promoting-the-deubiquitination-of-pcna
#13
Fei Li, Bin Liu, Xiaolan Zhou, Quan Xu
DNA damage response induced by ionizing radiation (IR) is an important event that involved in the sensitivity and efficiency of radiotherapy in human medulloblastoma. RNF8 is a E3 ubiquitin ligase and has key roles in the process of DNA damage and repair. Our study aimed to evaluate the effect of RNF8 in the DNA damage repair induced by IR exposure in medulloblastoma cells. We found that the levels of RNF8 were significantly up-regulated by γ-ray irradiation in a dose-dependent manner in medulloblastoma cells, and colocalized with γ-H2AX, a sensitive marker of DNA double strand break induced by γ-ray radiation...
January 10, 2018: Oncology Research
https://www.readbyqxmd.com/read/29320576/targeting-dna-repair-with-pnkp-inhibition-sensitizes-radioresistant-prostate-cancer-cells-to-high-let-radiation
#14
Pallavi Srivastava, Asitikantha Sarma, Chandra Mohini Chaturvedi
High linear energy transfer (LET) radiation or heavy ion such as carbon ion radiation is used as a method for advanced radiotherapy in the treatment of cancer. It has many advantages over the conventional photon based radiotherapy using Co-60 gamma or high energy X-rays from a Linear Accelerator. However, charged particle therapy is very costly. One way to reduce the cost as well as irradiation effects on normal cells is to reduce the dose of radiation by enhancing the radiation sensitivity through the use of a radiomodulator...
2018: PloS One
https://www.readbyqxmd.com/read/29317830/quercetin-suppresses-dna-double-strand-break-repair-and-enhances-the-radiosensitivity-of-human-ovarian-cancer-cells-via-p53-dependent-endoplasmic-reticulum-stress-pathway
#15
Cheng Gong, Zongyuan Yang, Lingyun Zhang, Yuehua Wang, Wei Gong, Yi Liu
Quercetin is proven to have anticancer effects for many cancers. However, the role of tumor suppressor p53 on quercetin's radiosensitization and regulation of endoplasmic reticulum (ER) stress response in this process remains obscure. Here, quercetin exposure resulted in ER stress, prolonged DNA repair, and the expression of p53 protein; phosphorylation on serine 15 and 20 increased in combination with X-irradiation. Quercetin pretreatment could potentiate radiation-induced cell death. The combination of irradiation and quercetin treatment aggravated DNA damages and caused typical apoptotic cell death; as well the expression of Bax and p21 elevated and the expression of Bcl-2 decreased...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29316551/chloroquine-enhances-the-radiosensitivity-of-bladder-cancer-cells-by-inhibiting-autophagy-and-activating-apoptosis
#16
Feng Wang, Jinyuan Tang, Pengchao Li, Shuhui Si, Hao Yu, Xiao Yang, Jun Tao, Qiang Lv, Min Gu, Haiwei Yang, Zengjun Wang
BACKGROUND/AIMS: Chloroquine was formerly used as an anti-malarial agent drug but has now been proven to be useful for various diseases. This study aimed to investigate the radiosensitizing effect of chloroquine in bladder cancer, with an emphasis on autophagy inhibition and apoptosis induction. METHODS: Bladder cancer cell lines were irradiated with or without chloroquine. Cell proliferation was determined by a Cell Counting Kit 8 assay. The radiosensitization effect of chloroquine was evaluated by clonogenic survival and progression of xenograft tumors...
December 22, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29309248/faster-development-covaries-with-higher-dna-damage-in-grasshoppers-chorthippus-albomarginatus-from-chernobyl
#17
Andrea Bonisoli-Alquati, Shanna Ostermiller, De Anna E Beasley, Shane M Welch, Anders P Møller, Timothy A Mousseau
In Chernobyl, chronic exposure to radioactive contaminants has a variety of deleterious effects on exposed organisms, including genetic damage and mutation accumulation. However, the potential for such effects to be transmitted to the next generation is poorly understood. We captured lesser marsh grasshoppers (Chorthippus albomarginatus) in the Chernobyl Exclusion Zone from sites varying in levels of environmental radiation by more than three orders of magnitude. We then raised their offspring in a common garden experiment in order to assess the effects of parental exposure to radiation on offspring development and DNA damage...
March 2018: Physiological and Biochemical Zoology: PBZ
https://www.readbyqxmd.com/read/29301085/adventures-in-scaffold-morphing-discovery-of-fused-ring-heterocyclic-checkpoint-kinase-1-chk1-inhibitors
#18
Bin Yang, Melissa Vasbinder, Alexander W Hird, Qibin Su, Haixia Wang, Yan Yu, Dorin Toader, Paul D Lyne, Jon A Read, Jason Breed, Stephanos Ioannidis, Chun Deng, Michael Grondine, Nancy DeGrace, David Whitston, Patrick Brassil, James W Janetka
Checkpoint kinase-1 (CHK1) inhibitors are potential cancer therapeutics which can be utilized for enhancing the efficacy of DNA damaging agents. Multiple small molecule CHK1 inhibitors from different chemical scaffolds have been developed and evaluated in clinical trials in combination with chemotherapeutics and radiation treatment. Scaffold morphing of thiophene carboxamide ureas (TCUs), such as AZD7762 (1) and a related series of triazoloquinolines (TZQs), led to the identification of fused-ring bicyclic CHK1 inhibitors, 7-carboxamide thienopyridines (7-CTPs) and 7-carboxamide indoles...
January 4, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29300773/the-effect-of-well-characterized-very-low-dose-x-ray-radiation-on-fibroblasts
#19
Katelyn Truong, Suzanne Bradley, Bryana Baginski, Joseph R Wilson, Donald Medlin, Leon Zheng, R Kevin Wilson, Matthew Rusin, Endre Takacs, Delphine Dean
The purpose of this study is to determine the effects of low-dose radiation on fibroblast cells irradiated by spectrally and dosimetrically well-characterized soft x-rays. To achieve this, a new cell culture x-ray irradiation system was designed. This system generates characteristic fluorescent x-rays to irradiate the cell culture with x-rays of well-defined energies and doses. 3T3 fibroblast cells were cultured in cups with Mylar® surfaces and were irradiated for one hour with characteristic iron (Fe) K x-ray radiation at a dose rate of approximately 550 μGy/hr...
2018: PloS One
https://www.readbyqxmd.com/read/29296039/modulation-of-radiation-induced-base-excision-repair-pathway-gene-expression-by-melatonin
#20
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
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