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h2ax and irradiation

Yang Chen, Youyou Wang, Lujun Zhao, Ping Wang, Jifeng Sun, Rudi Bao, Chenghai Li, Ningbo Liu
Objective: To investigate the potential of HS-10182, a second-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), as a radiosensitizer in non-small cell lung cancer (NSCLC). Methods: Two cell lines of NSCLCs, A549 that possesses wild-type (WT) EGFRs and H1975 that possesses EGFR L858R/T790M double mutations, were treated with HS-10182 at various concentrations, and cell viabilities were determined using the MTS assay. The cells were tested by clonogenic survival assays to identify the radiosensitivity of both groups...
February 2018: Cancer Biology & Medicine
Sirimanas Jiaranuchart, Atsushi Kaida, Yusuke Onozato, Hiroyuki Harada, Masahiko Miura
OBJECTIVE: The objective of this study was to characterize the DNA damage response in two human oral cancer cell lines following X-irradiation. DESIGN: To visualize radiation-induced cell cycle alterations, two human oral cancer cell lines, HSC3 and HSC4, expressing fluorescent ubiquitination-based cell cycle indicator (Fucci) were established in this study. G2 arrest kinetics following irradiation were obtained from two-color flow cytometric analysis and pedigrees of Fucci fluorescence...
March 6, 2018: Archives of Oral Biology
F Berardinelli, A Sgura, A Facoetti, S Leone, B Vischioni, M Ciocca, A Antoccia
The pentacyclic acridine RHPS4 is a highly potent and specific G-quadruplex (G4) ligand, which binds and stabilizes telomeric G4 leading to the block of the replication forks at telomeres and consequently to telomere dysfunctionalization. In turn, the cell recognizes unprotected telomeres as DNA double-strand breaks with consequent activation of DNA repair response at telomeres, cellular growth impairment and death. Data from the literature showed the capability of this compound to sensitize U251MG glioblastoma radioresistant cell line to X-rays sparsely ionizing radiations...
February 27, 2018: FEBS Journal
Hideaki Nakamura, Hidemasa Bono, Keiko Hiyama, Takeshi Kawamoto, Yukio Kato, Takeshi Nakanishi, Masahiko Nishiyama, Eiso Hiyama, Nobuyuki Hirohashi, Eisaburo Sueoka, Lorenz Poellinger, Keiji Tanimoto
Tumor hypoxia contributes to a biologically aggressive phenotype and therapeutic resistance. Recent studies have revealed that hypoxia reduces expression of several DNA damage recognition and repair (DRR) genes via both hypoxia-inducible factor (HIF)-independent and -dependent pathways, and this induced genomic instability in cancer cells. We show here that one of the HIF-target genes-differentiated embryo chondrocyte (DEC)-plays a role in DNA damage response via transcriptional repression. Comprehensive gene expression and database analyses have revealed systemic repression of DNA-DRR genes in cancer and non-cancer cells under hypoxic conditions...
2018: PloS One
Akshaykumar A Nayak, Kamalesh Dattaram Mumbrekar, B S Satish Rao
In a scenario of accidental mass radiation exposure transportation and analysis of samples may take some time, resulting in loss of biomarker information over this period. The present study aims to use phosphatase inhibitors for longer retention of focal signals to adopt γ-H2AX as a biodosimetric biomarker for the management of early triage. Peripheral blood lymphocytes isolated from healthy individuals were irradiated in vitro with x-rays and γ-H2AX foci were analysed using fluorescent microscopy and flow cytometric methods...
February 15, 2018: Journal of Radiological Protection: Official Journal of the Society for Radiological Protection
Michael Hausmann, Emma Wagner, Jin-Ho Lee, Gerrit Schrock, Wladimir Schaufler, Matthias Krufczik, Franziska Papenfuß, Matthias Port, Felix Bestvater, Harry Scherthan
Ionizing radiation (IR)-induced damage confers functional and conformational changes to nuclear chromatin associated with DNA single and double strand breaks. This leads to the activation of complex DNA repair machineries that aim to preserve the integrity of the DNA molecule. Since hetero- and euchromatin are differentially accessible to DNA repair pathways, local chromatin re-arrangements and structural changes are among the consequences of an activated DNA damage response. Using super-resolution localization microscopy (SRLM), we investigated the X-ray-induced repositioning of γ-H2AX and histone H3K9me3 heterochromatin marks in the nuclei of HeLa cells...
February 14, 2018: Nanoscale
Ariungerel Gerelchuluun, Junko Maeda, Eri Manabe, Colleen A Brents, Takeji Sakae, Akira Fujimori, David J Chen, Koji Tsuboi, Takamitsu A Kato
Suberoylanilide hydroxamic acid (SAHA) is a histone deacetylase inhibitor, which has been widely utilized throughout the cancer research field. SAHA-induced radiosensitization in normal human fibroblasts AG1522 and lung carcinoma cells A549 were evaluated with a combination of γ-rays, proton, and carbon ion exposure. Growth delay was observed in both cell lines during SAHA treatment; 2 μM SAHA treatment decreased clonogenicity and induced cell cycle block in G1 phase but 0.2 μM SAHA treatment did not show either of them...
February 7, 2018: International Journal of Molecular Sciences
Ricardo Cortez Cardoso Penha, Simona Pellecchia, Roberto Pacelli, Luis Felipe Ribeiro Pinto, Alfredo Fusco
BACKGROUND: Ionizing Radiation (IR) is a well-known risk factor for papillary thyroid cancer, and it has been reported to deregulate microRNA expression, which is important to thyroid carcinogenesis. Therefore, we have investigated the impact of IR on microRNA expression profile of the normal thyroid cell line (FRTL-5 CL2) and as well as its effect on radiosensitivity of thyroid cancer cell lines, especially the human anaplastic thyroid carcinoma cell line (8505c). METHODS: The global microRNA expression profile of irradiated FRTL-5 CL2 cells (5 Gy X-ray) was characterized and data were confirmed by qRT-PCR evaluating the expression of rno-miR-10b-5p, rno-miR-33-5p, rno-miR-128-1-5p, rno-miR-199a-3p, rno-miR-296-5p, rno-miR-328a-3p and rno-miR-541-5p in irradiated cells...
February 3, 2018: Thyroid: Official Journal of the American Thyroid Association
Sarah Schumann, Uta Eberlein, Razan Muhtadi, Michael Lassmann, Harry Scherthan
Irradiation with high linear energy transfer α-emitters, like the clinically used Ra-223 dichloride, severely damages cells and induces complex DNA damage including closely spaced double-strand breaks (DSBs). As the hematopoietic system is an organ-at-risk for the treatment, knowledge about Ra-223-induced DNA damage in blood leukocytes is highly desirable. Therefore, 36 blood samples from six healthy volunteers were exposed ex-vivo (in solution) to different concentrations of Ra-223. Absorbed doses to the blood were calculated assuming local energy deposition of all α- and β-particles of the decay, ranging from 0 to 142 mGy...
February 2, 2018: Scientific Reports
Marion Eryilmaz, Eberhard Schmitt, Matthias Krufczik, Franziska Theda, Jin-Ho Lee, Christoph Cremer, Felix Bestvater, Wladimir Schaufler, Michael Hausmann, Georg Hildenbrand
In radiation biophysics, it is a subject of nowadays research to investigate DNA strand break repair in detail after damage induction by ionizing radiation. It is a subject of debate as to what makes up the cell's decision to use a certain repair pathway and how the repair machinery recruited in repair foci is spatially and temporarily organized. Single-molecule localization microscopy (SMLM) allows super-resolution analysis by precise localization of single fluorescent molecule tags, resulting in nuclear structure analysis with a spatial resolution in the 10 nm regime...
January 22, 2018: Cancers
Li Liao, Wen-Jing Yan, Chun-Mei Tian, Mao-Yu Li, Yong-Quan Tian, Gu-Qing Zeng
Radiotherapy is the primary treatment for nasopharyngeal carcinoma while radioresistance can hinder efficient treatment. To explore the role of annexin A1 and its potential mechanisms in radioresistance of nasopharyngeal carcinoma, human nasopharyngeal carcinoma cell line CNE2-sh annexin A1 (knockdown of annexin A1) and the control cell line CNE2-pLKO.1 were constituted and CNE2-sh annexin A1 xenograft mouse model was generated. The effect of annexin A1 knockdown on the growth of xenograft tumor after irradiation and radiation-induced DNA damage and repair was analyzed...
January 1, 2018: Technology in Cancer Research & Treatment
Akshaykumar A Nayak, Kamalesh Dattaram Mumbrekar, Satish Rao
In a scenario of accidental mass radiation exposure, transportation and analyzing samples may take its time resulting in loss of biomarker information over this period. The present study aims to use phosphatases inhibitors for longer retention of foci signals to adopt γ-H2AX as a biodosimetric biomarker for the management of early triage. Peripheral blood lymphocytes isolated from healthy individuals irradiated in vitro with X-rays, and γ-H2AX analysed using fluorescent microscopy and flow cytometric methods...
January 22, 2018: Journal of Radiological Protection: Official Journal of the Society for Radiological Protection
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
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
Erminia Fardone, Benoît Pouyatos, Elke Bräuer-Krisch, Stefan Bartzsch, Hervè Mathieu, Herwig Requardt, Domenico Bucci, Giacomo Barbone, Paola Coan, Giuseppe Battaglia, Geraldine Le Duc, Alberto Bravin, Pantaleo Romanelli
Synchrotron-generated microplanar beams (microbeams) provide the most stereo-selective irradiation modality known today. This novel irradiation modality has been shown to control seizures originating from eloquent cortex causing no neurological deficit in experimental animals. To test the hypothesis that application of microbeams in the hippocampus, the most common source of refractory seizures, is safe and does not induce severe side effects, we used microbeams to induce transections to the hippocampus of healthy rats...
January 9, 2018: Scientific Reports
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
Jun Wang, Lihong Chang, Xiaoping Lai, Xia Li, Zhiyuan Wang, Zizhen Huang, Jiancong Huang, Gehua Zhang
The increasing resistance of nasopharyngeal carcinoma to irradiation makes the exploration of effective radiosensitizers necessary. Tetrandrine is known to be an antitumor drug, but little is known regarding its radiosensitization effect on nasopharyngeal carcinoma. We investigated the effect of combined treatment of irradiation and maximum non-cytotoxic doses of tetrandrine on the nasopharyngeal carcinoma cell lines CNE1 and CNE2. The maximum non-cytotoxic doses of tetrandrine in CNE1 and CNE2 cells were assessed using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay...
December 29, 2017: Cell Cycle
Julie Bensimon Etzol, Marco Valente, Sandrine Altmeyer, Caroline Bettencourt, Samuel Bouvet, Guillaume Cosler, François Desangles, Michel Drouet, Fabrice Entine, Francis Hérodin, Flora Jourquin, Yannick Lecompte, Patrick Martigne, Xavier Michel, Jérôme Pateux, Nicolas Ugolin, Sylvie Chevillard
DosiKit is a new field-radiation biodosimetry immunoassay for rapid triage of individuals exposed to external total-body radiation. Here, we report on the validation of this immunoassay in human blood cell extracts 0.5 h after in vitro exposure to137 Cs gamma rays, using γ-H2AX analysis. First, calibration curves were established for five donors at doses ranging from 0 to 10 Gy and dose rates ranging from ∼0.8 to ∼3 Gy/min. The calibration curves, together with a γ-H2AX peptide scale, enabled the definition of inter-experimental correction factors...
December 7, 2017: Radiation Research
Zhen Yang, Qing-De Wa, Chao Lu, Wei Pan, Zi-Μo Lu, Jun Ao
Osteosarcoma is a kind of high-risk sarcoma of the skeleton typically observed in people under 25 years old. Currently, radiotherapy is widely applied in cancer treatment. However, osteosarcoma is radioresistant and accordingly new, more effective radiosensitizers are needed. miRNAs have been reported to play an important role in osteosarcoma radiosensitivity. We examined the modulating effect of miR‑328‑3p in vivo and in vitro. miR‑328‑3p was downregulated in HOS‑2R cells. The overexpression of miR‑328‑3p enhanced the radiosensitivity of osteosarcoma cells...
February 2018: Oncology Reports
Winson S Ho, Saman Sizdahkhani, Shuyu Hao, Hua Song, Ashlee Seldomridge, Anita Tandle, Dragan Maric, Tamalee Kramp, Rongze Lu, John D Heiss, Kevin Camphausen, Mark R Gilbert, Zhengping Zhuang, Deric M Park
Atypical and anaplastic meningiomas (AAM) represent 20% of all meningiomas. They are associated with poor outcomes due to their tendency to recur. While surgery and radiation (RT) are first line therapy, no effective systemic medical treatment has been identified. Protein phosphatase 2A (PP2A) is a ubiquitously expressed serine/threonine phosphatase involved in cell cycle regulation and DNA repair. Here, we examined radiosensitizing effects of LB-100, a novel inhibitor of PP2A against AAM as a novel treatment strategy...
February 28, 2018: Cancer Letters
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