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https://www.readbyqxmd.com/read/28212705/detection-of-dna-damage-by-space-radiation-in-human-fibroblasts-flown-on-the-international-space-station
#1
Tao Lu, Ye Zhang, Michael Wong, Alan Feiveson, Ramona Gaza, Nicholas Stoffle, Huichen Wang, Bobby Wilson, Larry Rohde, Louis Stodieck, Fathi Karouia, Honglu Wu
Although charged particles in space have been detected with radiation detectors on board spacecraft since the discovery of the Van Allen Belts, reports on the effects of direct exposure to space radiation in biological systems have been limited. Measurement of biological effects of space radiation is challenging due to the low dose and low dose rate nature of the radiation environment, and due to the difficulty in distinguishing the radiation effects from microgravity and other space environmental factors. In astronauts, only a few changes, such as increased chromosome aberrations in their lymphocytes and early onset of cataracts, are attributed primarily to their exposure to space radiation...
February 2017: Life Sciences in Space Research
https://www.readbyqxmd.com/read/28195382/contribution-of-atm-and-atr-kinase-pathways-to-p53-mediated-response-in-etoposide-and-methyl-methanesulfonate-induced-dna-damage
#2
Bin Sun, Susan M Ross, Sean Rowley, Yeyejide Adeleye, Rebecca A Clewell
p53 is a key integrator of cellular response to DNA damage, supporting post-translational repair and driving transcription-mediated responses including cell cycle arrest, apoptosis, and repair. DNA damage sensing kinases recognize different types of DNA damage and initiate specific responses through various post-translational modifications of p53. This study evaluated chemical specificity of the p53 pathway response by manipulating p53 or its upstream kinases and assessing the effect on DNA damage and cellular responses to prototype chemicals: etoposide (ETP, topoisomerase II inhibitor) and methyl methane sulfonate (MMS, alkylating agent)...
February 14, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28194454/in-vitro-genotoxicity-of-carcinogenic-asarone-isomers
#3
S Haupenthal, K Berg, M Gründken, S Vallicotti, M Hemgesberg, K Sak, D Schrenk, M Esselen
The present study focused on genotoxic properties of the carcinogenic phenylpropanoids α-asarone and β-asarone, which are found in several herbs and spices, such as Acorus calamus or Acorus gramineus. Cytotoxic and genotoxic effects were determined in human liver carinoma HepG2 cells, in hamster lung fibroblast V79 cells and in human cytochrome P450 1A2 and human sulfotransferase 1C2 transfected V79 cells (tV79). The Alamar blue assay was used to measure cytotoxicity of both isomers prior to the identification of DNA damaging properties by single cell gel electrophoresis (comet assay)...
February 14, 2017: Food & Function
https://www.readbyqxmd.com/read/28192606/metformin-alleviates-aging-cellular-phenotypes-in-hutchinson-gilford-progeria-syndrome-dermal-fibroblasts
#4
Seul-Ki Park, Ok Sarah Shin
Metformin is a popular antidiabetic biguanide, which has been considered as a candidate drug for cancer treatment and aging prevention. Hutchinson-Gilford progeria syndrome (HGPS) is a devastating disease characterized by premature aging and severe age-associated complications leading to death. The effects of metformin on HGPS dermal fibroblasts remain largely undefined. In this study, we investigated whether metformin could exert a beneficial effect on nuclear abnormalities and delay senescence in fibroblasts derived from HGPS patients...
February 13, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28187758/photodynamic-therapy-combined-to-cisplatin-potentiates-cell-death-responses-of-cervical-cancer-cells
#5
Laura Marise de Freitas, Rodolfo Bortolozo Serafim, Juliana Ferreira de Sousa, Thaís Fernanda Moreira, Cláudia Tavares Dos Santos, Amanda Martins Baviera, Valeria Valente, Christiane Pienna Soares, Carla Raquel Fontana
BACKGROUND: Photodynamic therapy (PDT) has proven to be a promising alternative to current cancer treatments, especially if combined with conventional approaches. The technique is based on the administration of a non-toxic photosensitizing agent to the patient with subsequent localized exposure to a light source of a specific wavelength, resulting in a cytotoxic response to oxidative damage. The present study intended to evaluate in vitro the type of induced death and the genotoxic and mutagenic effects of PDT alone and associated with cisplatin...
February 10, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28186131/recq1-helicase-is-involved-in-replication-stress-survival-and-drug-resistance-in-multiple-myeloma
#6
E Viziteu, B Klein, J Basbous, Y-L Lin, C Hirtz, C Gourzones, L Tiers, A Bruyer, L Vincent, C Grandmougin, A Seckinger, H Goldschmidt, A Constantinou, P Pasero, D Hose, J Moreaux
Multiple myeloma (MM) is a plasma cell cancer with poor survival, characterized by the expansion of multiple myeloma cells (MMCs) in the bone marrow. Using a microarray-based genome-wide screen for genes responding to DNA methyltransferases (DNMT) inhibition in MM cells, we identified RECQ1 among the most downregulated genes. RecQ helicases are DNA unwinding enzymes involved in the maintenance of chromosome stability. Here, we show that RECQ1 is significantly overexpressed in MMCs compared to normal plasma cells and that increased RECQ1 expression is associated with poor prognosis in three independent cohorts of patients...
February 10, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28185677/effects-of-antioxidants-on-dna-double-strand-breaks-in-human-gingival-fibroblasts-exposed-to-dental-resin-co-monomer-epoxy-metabolites
#7
Yang Yang, Xiuli He, Jianwei Shi, Reinhard Hickel, Franz-Xaver Reichl, Christof Högg
OBJECTIVE: Eluted dental resin co-monomers can be metabolized to intermediate methacrylic acid (MA) and, further, to epoxy metabolites. Antioxidants have been studied previously, with the intention of decreasing the DNA double-strand breaks (DNA-DSBs) in human gingival fibroblasts (HGFs). In this study, the effects of the antioxidants, ascorbic acid (Asc) and N-acetylcysteine (NAC), were investigated on co-monomer metabolite-induced DNA-DSBs. METHODS: HGFs were incubated with MA, 2,3-epoxy-2-methyl-propionicacid-methylester (EMPME) and 2,3-epoxy-2-methylpropionic acid (EMPA), respectively, in the presence or absence of antioxidants (Asc or NAC)...
February 6, 2017: Dental Materials: Official Publication of the Academy of Dental Materials
https://www.readbyqxmd.com/read/28185200/automated-high-content-screening-of-%C3%AE-h2ax-expression-in-hela-cells
#8
Nate Hopp, Jodi Hagen, Birte Aggeler, Alexander E Kalyuzhny
Due to their inherent nature, DNA strands can be easily broken by various environmental factors including chemical agents and ionizing radiation. Unrepaired DNA double-stranded breaks (DSBs) may result in genetic instability and have a strong negative impact on the integrity of the genome. It has been found that DSBs are always followed by phosphorylation of histone protein H2AX, a member of the H2A family, and immunocytochemical detection of phosphorylated H2AX (referred to as γ-H2AX) is one of the frequently used techniques for assessing DNA damage...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28185188/hapten-anti-hapten-technique-for-two-color-ihc-detection-of-phosphorylated-egfr-and-h2ax-using-primary-antibodies-raised-in-the-same-host-species
#9
Jodi Hagen, David Schwartz, Alexander E Kalyuzhny
Multiplex staining of cell and tissue sections with antibodies raised in the same host species is a serious challenge because of unwanted but inevitable cross-reactivity of secondary antibodies with irrelevant primary antibodies. Several techniques can be used to overcome this obstacle including direct labeling of primary antibodies with fluorescent tags and using tyramide signal amplification. Unfortunately these techniques either lack sensitivity, or require a long multistep protocol which can cause physical damage of specimens...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28184999/rosiglitazone-enhances-radiosensitivity-by-inhibiting-repair-of-dna-damage-in-cervical-cancer-cells
#10
Zhengzhe An, Jae-Ran Yu, Woo-Yoon Park
Radiation therapy (RT) is one of the main treatment modalities for cervical cancer. Rosiglitazone (ROSI) has been reported to have antiproliferative effects against various types of cancer cells and also to induce antioxidant enzymes that can scavenge reactive oxygen species (ROS) and thereby modify radiosensitivity. Here, we explored the effect of ROSI on radiosensitivity and the underlying mechanisms in cervical cancer cells. Three cervical cancer cell lines (ME-180, HeLa, and SiHa) were used. The cells were pretreated with ROSI and then irradiated...
February 9, 2017: Radiation and Environmental Biophysics
https://www.readbyqxmd.com/read/28181816/induction-of-oxidants-distinguishes-susceptibility-of-prostate-carcinoma-cell-lines-to-p53-gene-transfer-mediated-by-an-improved-adenoviral-vector
#11
Rodrigo E Tamura, Aline Hunger, Denise Fernandes, Francisco Laurindo, Eugenia Costanzi-Strauss, Bryan E Strauss
Previously, we developed an adenoviral vector, Ad-PG, where transgene expression is regulated by a p53-responsive promoter. When used to transfer the p53 cDNA, a positive feedback mechanism is established. Here we perform a critical comparison between Ad-PGp53 and AdRGD-PGp53, where the RGD motif was incorporated in the adenoviral fiber protein. AdRGD-PGp53 provided superior transgene expression levels and resulted in the killing of prostate carcinoma cell lines DU145 and PC3. In vitro, this effect was associated with increased production of cytoplasmic and mitochondrial oxidants, DNA damage as revealed by detection of phosphorylated H2AX as well as cell death consistent with apoptosis...
February 9, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28178195/overexpression-of-skp2-inhibits-the-radiation-induced-bystander-effects-of-esophageal-carcinoma
#12
Xiao-Chun Wang, Tie-Jun Zhang, Zi-Jian Guo, Chang-Yan Xiao, Xiao-Wen Ding, Fang Fang, Wen-Tao Sheng, Xu Shu, Jue Li
BACKGROUND: To investigate the effects of S-phase kinase protein 2 (SKP2) expression on the radiation induced bystander effect (RIBE) in esophageal cancer (EC) cells. MATERIALS AND METHODS: Western blot was used to detect the levels of SKP2, Rad51, and Ku70 in EC cells. Positive transfection, RNAi, micronucleus (MN), and γ-H2AX focus formation assay were used to investigate the effects of SKP2 on RIBE induced by irradiated cells. RESULTS: We found a significant negative correlation between SKP2 expression and MN frequency (p < 0...
February 6, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28166748/body-mass-index-modifies-the-relationship-between-%C3%AE-h2ax-a-dna-damage-biomarker-and-pathological-complete-response-in-triple-negative-breast-cancer
#13
Maddalena Barba, Patrizia Vici, Laura Pizzuti, Luigi Di Lauro, Domenico Sergi, Anna Di Benedetto, Cristiana Ercolani, Francesca Sperati, Irene Terrenato, Claudio Botti, Lucia Mentuccia, Laura Iezzi, Teresa Gamucci, Clara Natoli, Ilio Vitale, Marcella Mottolese, Ruggero De Maria, Marcello Maugeri-Saccà
BACKGROUND: Body mass index (BMI) is largely investigated as a prognostic and predictive factor in triple-negative breast cancer (TNBC). Overweight and obesity are linked to a variety of pathways regulating tumor-promoting functions, including the DNA damage response (DDR). The DDR physiologically safeguards genome integrity but, in a neoplastic background, it is aberrantly engaged and protects cancer cells from chemotherapy. We herein verified the role of BMI on a previously assessed association between DDR biomarkers and pathological complete response (pCR) in TNBC patients treated with neoadjuvant chemotherapy (NACT)...
February 6, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28165139/carboxylated-nanodiamonds-can-be-used-as-negative-reference-in-in-vitro-nanogenotoxicity-studies
#14
H Moche, V Paget, D Chevalier, E Lorge, N Claude, H A Girard, J C Arnault, S Chevillard, F Nesslany
Nanodiamonds (NDs) are promising nanomaterials for biomedical applications. However, a few studies highlighted an in vitro genotoxic activity for detonation NDs, which was not evidenced in one of our previous work quantifying γ-H2Ax after 20 and 100 nm high-pressure high-temperature ND exposures of several cell lines. To confirm these results, in the present work, we investigated the genotoxicity of the same 20 and 100 nm NDs and added intermediate-sized NDs of 50 nm. Conventional in vitro genotoxicity tests were used, i...
February 6, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28158293/phosphorylated-fraction-of-h2ax-as-a-measurement-for-dna-damage-in-cancer-cells-and-potential-applications-of-a-novel-assay
#15
Jiuping Ji, Yiping Zhang, Christophe E Redon, William C Reinhold, Alice P Chen, Laura K Fogli, Susan L Holbeck, Ralph E Parchment, Melinda Hollingshead, Joseph E Tomaszewski, Quentin Dudon, Yves Pommier, James H Doroshow, William M Bonner
Phosphorylated H2AX (γ-H2AX) is a sensitive marker for DNA double-strand breaks (DSBs), but the variability of H2AX expression in different cell and tissue types makes it difficult to interpret the meaning of the γ-H2AX level. Furthermore, the assays commonly used for γ-H2AX detection utilize laborious and low-throughput microscopy-based methods. We describe here an ELISA assay that measures both phosphorylated H2AX and total H2AX absolute amounts to determine the percentage of γ-H2AX, providing a normalized value representative of the amount of DNA damage...
2017: PloS One
https://www.readbyqxmd.com/read/28156042/double-strand-dna-breaks-induced-by-paracyclophane-gold-i-complexes
#16
Peter Werner Roesky, Sebastian Bestgen, Carmen Seidl, Thomas Wiesner, Andreas Zimmer, Martina Falk, Beate Köberle, Martina Austeri, Jan Paradies, Stefan Bräse, Ute Schepers
Gold(I) complexes of ClickPhos [2.2]paracyclophane ligands were synthesized in excellent yields and fully characterized by spectroscopic methods as well as X-ray crystallography. The complexes exhibit a rigid ligand backbone and a triazolyl moiety and were systematically studied with respect to their cytotoxic properties. In combination with the ionic complex [(GemPhos)Au(tht)][ClO4] (tht = tetrahydrothiophene), in which the gold(I) atom exhibits a distorted trigonal coordination sphere of two phosphines and a labile tht ligand, their efficiency in cytotoxicity was investigated in HeLa, MCF7, and HCT116 cells as well as in a Zebra fish model...
February 3, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28125685/lack-of-casein-kinase-1-delta-promotes-genomic-instability-the-accumulation-of-dna-damage-and-down-regulation-of-checkpoint-kinase-1
#17
Yoshimi Endo Greer, Bo Gao, Yingzi Yang, Andre Nussenzweig, Jeffrey S Rubin
Casein kinase 1 delta (CK1δ) is a conserved serine/threonine protein kinase that regulates diverse cellular processes. Mice lacking CK1δ have a perinatal lethal phenotype and typically weigh 30% less than their wild type littermates. However, the causes of death and small size are unknown. We observed cells with abnormally large nuclei in tissue from Csnk1d null embryos, and multiple centrosomes in mouse embryo fibroblasts (MEFs) deficient in CK1δ (MEFCsnk1d null). Results from γ-H2AX staining and the comet assay demonstrated significant DNA damage in MEFCsnk1d null cells...
2017: PloS One
https://www.readbyqxmd.com/read/28111726/ganetespib-overcomes-resistance-to-parp-inhibitors-in-breast-cancer-by-targeting-core-proteins-in-the-dna-repair-machinery
#18
Juhong Jiang, Yuanzhi Lu, Zhi Li, Liping Li, Daoli Niu, Wenwei Xu, Jing Liu, Lin Fu, Ziqing Zhou, Yingying Gu, Fen Xia
DNA damage repair plays essential roles in drug resistance, especially resistance to Poly (ADP-ribose) polymerase (PARP) inhibitors in the clinic. A subset of DNA repair proteins such as Breast cancer gene 1 (BRCA1), BRCA2 and RecA homolog (RAD51) are client proteins of heat shock protein 90 (Hsp90). Clearance of these DNA repair proteins by inhibition of Hsp90 is a promising strategy for overcoming resistance to PARP inhibitors. Here we report the pharmacological analysis of the highly potent second-generation Hsp90 inhibitor, ganetespib...
January 23, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28108515/prostate-cancer-patients-with-late-radiation-toxicity-exhibit-reduced-expression-of-genes-involved-in-dna-double-strand-break-repair-and-homologous-recombination
#19
Bregje van Oorschot, Lon Uitterhoeve, Ilja Oomen, Rosemarie Ten Cate, Jan Paul Medema, Harry Vrieling, Lukas J A Stalpers, Perry D Moerland, Nicolaas A P Franken
Severe late damage to normal tissue is a major limitation of cancer radiotherapy in prostate cancer patients. In a recent retrospective study, late radiation toxicity was found to relate to a decreased decay of γ-H2AX foci and reduced induction of DNA double strand break repair genes. Here we report evidence of prognostic utility in prostate cancer for γ-H2AX foci decay ratios and gene expression profiles derived from ex vivo-irradiated patient lymphocytes. Patients were followed ≥2 years after radiotherapy...
January 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28107384/an-approach-to-elucidate-nbs1-function-in-dna-repair-using-frequent-nonsynonymous-polymorphism-in-wild-medaka-oryzias-latipes-populations
#20
Kento Igarashi, Junya Kobayashi, Takafumi Katsumura, Yusuke Urushihara, Kyohei Hida, Tomomi Watanabe-Asaka, Hiroki Oota, Shoji Oda, Hiroshi Mitani
Nbs1 is one of the genes responsible for Nijmegen breakage syndrome, which is marked with high radiosensitivity. In human NBS1 (hNBS1), Q185E polymorphism is known as the factor to cancer risks, although its DSB repair defect has not been addressed. Here we investigated the genetic variations in medaka (Oryzias latipes) wild populations, and found 40 nonsynonymous single nucleotide polymorphisms (SNPs) in medaka nbs1 (olnbs1) gene within 5 inbred strains. A mutation to histidine in Q170 residue in olNbs1, which corresponds to Q185 residue of hNBS1, was widely distributed in the closed colonies derived from the eastern Korean population of medaka...
2017: PloS One
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