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Dna damage and cancer

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https://www.readbyqxmd.com/read/29792945/cross-linking-by-epichlorohydrin-and-diepoxybutane-correlates-with-cytotoxicity-and-leads-to-apoptosis-in-human-leukemia-hl-60-cells
#1
Phuong M Le, Vanesa L Silvestri, Samuel C Redstone, Jordanne B Dunn, Julie T Millard
The bifunctional alkylating agents epichlorohydrin (ECH) and diepoxybutane (DEB) have been linked to increased cancer risks in industrial workers. These compounds react with DNA and proteins, leading to genotoxic effects. We used the comet assay to monitor formation of cross-links in HL-60 cells treated with ECH, DEB, and the structurally related anti-cancer drug mechlorethamine (HN2). We report a time- and dose-dependent cytotoxicity that correlated with cross-linking activity, following the order HN2 > DEB > ECH...
May 21, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29790588/the-lncrna-casc9-and-rna-binding-protein-hnrnpl-form-a-complex-and-co-regulate-genes-linked-to-akt-signaling
#2
Marcel Klingenberg, Matthias Groß, Ashish Goyal, Maria Polycarpou-Schwarz, Thilo Miersch, Anne-Sophie Ernst, Jörg Leupold, Nitin Patil, Uwe Warnken, Heike Allgayer, Thomas Longerich, Peter Schirmacher, Michael Boutros, Sven Diederichs
The identification of viability-associated long non-coding RNAs (lncRNA) might be a promising rationale for new therapeutic approaches in liver cancer. Here, we applied the first RNAi screening approach in hepatocellular carcinoma (HCC) cell lines to find viability-associated lncRNAs. Among the multiple identified lncRNAs with a significant impact on HCC cell viability, we selected CASC9 (Cancer Susceptibility 9) due to the strength of its phenotype, expression, and upregulation in HCC versus normal liver. CASC9 regulated viability across multiple HCC cell lines as shown by CRISPR interference, single siRNA- and siPOOL-mediated depletion of CASC9...
May 23, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29790536/dna-interactions-of-non-chelating-tinidazole-based-coordination-compounds-and-their-structural-redox-and-cytotoxic-properties
#3
Rodrigo Castro-Ramírez, Naytzé Ortiz-Pastrana, Ana B Caballero, Matthew T Zimmerman, Bradley S Stadelman, Andrea A E Gaertner, Julia L Brumaghim, Luís Korrodi-Gregório, Ricardo Pérez-Tomás, Patrick Gamez, Norah Barba-Behrens
Novel tinidazole (tnz) coordination compounds of different geometries were synthesised, whose respective solid-state packing appears to be driven by inter- and intramolecular lone pairπ interactions. The copper(ii) compounds exhibit interesting redox properties originating from both the tnz and the metal ions. These complexes interact with DNA through two distinct ways, namely via electrostatic interactions or/and groove binding, and they can mediate the generation of ROS that damage the biomolecule. Cytotoxic studies revealed an interesting activity of the dinuclear compound [Cu(tnz)2(μ-Cl)Cl]2 7, which is further more efficient towards cancer cells, compared with normal cells...
May 23, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/29790063/in-vitro-and-in-vivo-evaluation-of-antitumor-activity-of-ligustrum-robustum-a-chinese-herbal-tea
#4
Hao-Jiang Zuo, Shan Liu, Chun Yan, Li-Man Li, Xiao-Fang Pei
OBJECTIVE: To examine the effect of the aqueous extract of Ligustrum robustum on tumor growth in vitro and in vivo and explore the possible molecular mechanisms. METHODS: In in vitro study, cell viabilities of human cervical carcinoma cells (HeLa), human breast cancer cells (MCF-7), human prostate cancer cells (PC-3), human hepatoma cells (7721) and human colon carcinoma cells (SW480) were evaluated with cell counting kit-8. For L. robustum-treated Hela cells, early or late apoptosis were evaluated by annexin V/PI staining...
May 22, 2018: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/29789556/foxm1-dependent-rad51-and-brca2-signaling-protects-idiopathic-pulmonary-fibrosis-fibroblasts-from-radiation-induced-cell-death
#5
Jintaek Im, Jessica Lawrence, Davis Seelig, Richard S Nho
Radiation therapy is critical for the control of many tumors and lung is an important dose-limiting organ that impacts radiation dose prescribed to avoid irreversible pulmonary fibrosis in cancer survivors. Idiopathic pulmonary fibrosis (IPF) is a chronic, irreversible lung disease caused by aberrantly activated lung (myo)fibroblasts. The presence of pro-fibrotic, apoptosis-resistant fibroblasts in IPF promotes progressive fibrosis and may have a role in other diseases, if these resistant cells are selected for as a consequence of treatment...
May 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29789392/fam35a-associates-with-rev7-and-modulates-dna-damage-responses-of-normal-and-brca1-defective-cells
#6
Junya Tomida, Kei-Ichi Takata, Sarita Bhetawal, Maria D Person, Hsueh-Ping Chao, Dean G Tang, Richard D Wood
To exploit vulnerabilities of tumors, it is urgent to identify associated defects in genome maintenance. One unsolved problem is the mechanism of regulation of DNA double-strand break repair by REV7 in complex with 53BP1 and RIF1, and its influence on repair pathway choice between homologous recombination and non-homologous end-joining. We searched for REV7-associated factors in human cells and found FAM35A, a previously unstudied protein with an unstructured N-terminal region and a C-terminal region harboring three OB-fold domains similar to single-stranded DNA-binding protein RPA, as novel interactor of REV7/RIF1/53BP1...
May 22, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29789391/mst2-kinase-suppresses-rdna-transcription-in-response-to-dna-damage-by-phosphorylating-nucleolar-histone-h2b
#7
Dafni Eleftheria Pefani, Maria Laura Tognoli, Deniz Pirincci Ercan, Vassilis Gorgoulis, Eric O'Neill
The heavily transcribed rDNA repeats that give rise to the ribosomal RNA are clustered in a unique chromatin structure, the nucleolus. Due to its highly repetitive nature and transcriptional activity, the nucleolus is considered a hotspot of genomic instability. Breaks in rDNA induce a transient transcriptional shut down to conserve energy and promote rDNA repair; however, how nucleolar chromatin is modified and impacts on rDNA repair is unknown. Here, we uncover that phosphorylation of serine 14 on histone H2B marks transcriptionally inactive nucleolar chromatin in response to DNA damage...
May 22, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29788781/purines-and-triazolo-4-3-e-purines-containing-pyrazole-moiety-as-potential-anticancer-and-antioxidant-agents
#8
Omaima G Shaaban, Heba A Abd El Razik, Shams El-Dine A Shams El-Dine, Fawzia A Ashour, Alaa A El-Tombary, Ola S Afifi, Marwa M Abu-Serie
AIM: Targeting apoptosis regulators such as caspases aiming at inducing apoptosis is an attractive strategy in cancer therapy. MATERIALS & METHODS: 8-Substituted purine incorporating pyrazole moiety were designed, synthesized and evaluated for their anticancer and antioxidant activities. RESULTS: Compounds 7a and 8a displayed potent and selective anticancer activity against lung cancer A549 cell line with low cytotoxicity on peripheral blood mononuclear normal cells...
May 23, 2018: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/29788478/a-minimal-threshold-of-fancj-helicase-activity-is-required-for-its-response-to-replication-stress-or-double-strand-break-repair
#9
Sanjay Kumar Bharti, Joshua A Sommers, Sanket Awate, Marina A Bellani, Irfan Khan, Lynda Bradley, Graeme A King, Yeonee Seol, Venkatasubramanian Vidhyasagar, Yuliang Wu, Takuye Abe, Koji Kobayashi, Kazuo Shin-Ya, Hiroyuki Kitao, Marc S Wold, Dana Branzei, Keir C Neuman, Robert M Brosh
Fanconi Anemia (FA) is characterized by bone marrow failure, congenital abnormalities, and cancer. Of over 20 FA-linked genes, FANCJ uniquely encodes a DNA helicase and mutations are also associated with breast and ovarian cancer. fancj-/- cells are sensitive to DNA interstrand cross-linking (ICL) and replication fork stalling drugs. We delineated the molecular defects of two FA patient-derived FANCJ helicase domain mutations. FANCJ-R707C was compromised in dimerization and helicase processivity, whereas DNA unwinding by FANCJ-H396D was barely detectable...
May 21, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29787441/exome-sequencing-discloses-ionizing-radiation-induced-dna-variants-in-the-genome-of-human-gingiva-fibroblasts
#10
Neetika Nath, Jennifer Esche, Jessica Müller, Lars R Jensen, Matthias Port, Mario Stanke, Lars Kaderali, Harry Scherthan, Andreas W Kuss
Ionizing radiation can induce genomic lesions such as DNA double-strand breaks whose incomplete or faulty repair can result in mutations, which in turn can influence cellular functions and alter the fate of affected cells and organ systems. Ionizing-radiation-induced sequence alterations/mutations occur in a stochastic manner, which contributes to an increased cancer risk in irradiated individuals. Ionizing radiation exposure, and particularly acute doses at high dose rates (as often observed in radiation accidents), induce alterations in the genome that in part will reflect specific characteristics of the DNA damage response and the repair mechanisms involved...
July 2018: Health Physics
https://www.readbyqxmd.com/read/29787434/influence-of-confounding-factors-on-radiation-dose-estimation-using-in-vivo-validated-transcriptional-biomarkers
#11
Lourdes Cruz-Garcia, Grainne O'Brien, Ellen Donovan, Lone Gothard, Sue Boyle, Antoine Laval, Isabelle Testard, Lucyna Ponge, Grzegorz Woźniak, Leszek Miszczyk, Serge M Candéias, Elizabeth Ainsbury, Piotr Widlak, Navita Somaiah, Christophe Badie
For triage purposes following a nuclear accident, blood-based gene expression biomarkers can provide rapid dose estimates for a large number of individuals. Ionizing-radiation-responsive genes are regulated through the DNA damage-response pathway, which includes activation of multiple transcription factors. Modulators of this pathway could potentially affect the response of these biomarkers and consequently compromise accurate dose estimation calculations. In the present study, four potential confounding factors were selected: cancer condition, sex, simulated bacterial infection (lipopolysaccharide), and curcumin, an anti-inflammatory/antioxidant agent...
July 2018: Health Physics
https://www.readbyqxmd.com/read/29786770/the-extract-of-leonurus-sibiricus-transgenic-roots-with-atpap1-transcriptional-factor-induces-apoptosis-via-dna-damage-and-down-regulation-of-selected-epigenetic-factors-in-human-cancer-cells
#12
Przemysław Sitarek, Tomasz Kowalczyk, Simona Santangelo, Adam J Białas, Monika Toma, Joanna Wieczfinska, Tomasz Śliwiński, Ewa Skała
The aim of this study was to determine the anticancer potential of Leonurus sibiricus extract derived from in vitro transgenic roots transformed by Agrobacetrium rhizogenes with AtPAP1 transcriptional factor, and that of transformed roots without construct, on grade IV human glioma cells and the U87MG cell line, and attempt to characterize the mechanism involved in this process. The anticancer effect induced by the tested extracts was associated with DNA damage, PARP cleavage/increased H2A.X histone levels and UHRF-1/DNMT1 down-regulation of mRNA levels...
May 21, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29784358/short-probe-based-duplex-specific-nuclease-signal-amplification-strategy-enables-imaging-of-endogenous-micrornas-in-living-cells-with-ultrahigh-specificity
#13
Yingjun Ma, Jun Chen, Danping Chen, Yuzhi Xu, Li Zhang, Zong Dai, Xiaoyong Zou
Specific nucleic acids amplification at a constant and mild temperature is important for imaging assay of endogenous microRNAs (miRNAs) in living cells. Duplex-specific nuclease (DSN) is attractive in one-step isothermal assay of miRNA; however, its intrinsic limitations of low amplification specificity and high reaction temperature greatly restrict the application scope. Herein, we present a short-probe-based DSN signal amplification (spDSNSA) strategy enabling analysis of miRNAs at body temperature with significantly high specificity...
August 15, 2018: Talanta
https://www.readbyqxmd.com/read/29784019/the-parp-inhibitor-olaparib-potentiates-the-effect-of-the-dna-damaging-agent-doxorubicin-in-osteosarcoma
#14
Hye Jeong Park, Jun Sang Bae, Kyoung Min Kim, Young Jae Moon, See-Hyoung Park, Sang Hoon Ha, Usama Khamis Hussein, Zhongkai Zhang, Ho Sung Park, Byung-Hyun Park, Woo Sung Moon, Jung Ryul Kim, Kyu Yun Jang
BACKGROUND: PARP1 facilitates the recovery of DNA-damaged cells by recruiting DNA damage response molecules such as γH2AX and BRCA1/2, and plays a role in resistance to antitumor therapies. Therefore, PARP inhibition being evaluated as an anti-cancer therapy. However, there are limited studies regrading PARP inhibition in osteosarcoma. METHODS: We evaluated the expression of DNA damage response molecules in 35 human osteosarcomas and investigated the effects of co-treatment of the PARP inhibitor, olaparib, and doxorubicin in osteosarcoma cells...
May 21, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29783721/azd1775-increases-sensitivity-to-olaparib-and-gemcitabine-in-cancer-cells-with-p53-mutations
#15
Xiangbing Meng, Jianling Bi, Yujun Li, Shujie Yang, Yuping Zhang, Mary Li, Haitao Liu, Yiyang Li, Megan E Mcdonald, Kristina W Thiel, Kuo-Kuang Wen, Xinhao Wang, Meng Wu, Kimberly K Leslie
Tumor suppressor p53 is responsible for enforcing cell cycle checkpoints at G1/S and G2/M in response to DNA damage, thereby allowing both normal and tumor cells to repair DNA before entering S and M. However, tumor cells with absent or mutated p53 are able to activate alternative signaling pathways that maintain the G2/M checkpoint, which becomes uniquely critical for the survival of such tumor cells. We hypothesized that abrogation of the G2 checkpoint might preferentially sensitize p53-defective tumor cells to DNA-damaging agents and spare normal cells with intact p53 function...
May 19, 2018: Cancers
https://www.readbyqxmd.com/read/29781987/retrospective-microrna-sequencing-complementary-dna-library-preparation-protocol-using-formalin-fixed-paraffin-embedded-rna-specimens
#16
Olivier Loudig, Christina Liu, Thomas Rohan, Iddo Z Ben-Dov
-Archived, clinically classified formalin-fixed paraffin-embedded (FFPE) tissues can provide nucleic acids for retrospective molecular studies of cancer development. By using non-invasive or pre-malignant lesions from patients who later develop invasive disease, gene expression analyses may help identify early molecular alterations that predispose to cancer risk. It has been well described that nucleic acids recovered from FFPE tissues have undergone severe physical damage and chemical modifications, which make their analysis difficult and generally requires adapted assays...
May 5, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29781764/charged-iron-particles-found-in-galactic-cosmic-rays-are-potent-inducers-of-epithelial-ovarian-tumors
#17
Birendra Mishra, Gregory W Lawson, Ryan Ripperdan, Laura Ortiz, Ulrike Luderer
Astronauts traveling in deep space are exposed to high-charge and energy (HZE) particles from galactic cosmic rays. We have previously determined that irradiation of adult female mice with iron HZE particles induces DNA double-strand breaks, oxidative damage and apoptosis in ovarian follicles, causing premature ovarian failure. These effects occur at lower doses than with conventional photon irradiation. Ovarian failure with resultant loss of negative feedback and elevated levels of gonadotropin hormones is thought to play a role in the pathophysiology of ovarian cancer...
May 21, 2018: Radiation Research
https://www.readbyqxmd.com/read/29777993/toenail-selenium-genetic-variation-in-selenoenzymes-and-risk-and-outcome-in-glioma
#18
Noah C Peeri, Jordan H Creed, Gabriella M Anic, Reid C Thompson, Jeffrey J Olson, Renato V LaRocca, Sajeel A Chowdhary, John D Brockman, Travis A Gerke, L Burton Nabors, Kathleen M Egan
BACKGROUND: Selenium is an essential trace element obtained through diet that plays a critical role in DNA synthesis and protection from oxidative damage. Selenium intake and polymorphisms in selenoproteins have been linked to the risk of certain cancers though data for glioma are sparse. METHODS: In a case-control study of glioma, we examined the associations of selenium in toenails and genetic variants in the selenoenzyme pathway with the risk of glioma and patient survival...
May 16, 2018: Cancer Epidemiology
https://www.readbyqxmd.com/read/29776024/simple-and-universal-model-for-electron-impact-ionization-of-complex-biomolecules
#19
Hong Qi Tan, Zhaohong Mi, Andrew A Bettiol
We present a simple and universal approach to calculate the total ionization cross section (TICS) for electron impact ionization in DNA bases and other biomaterials in the condensed phase. Evaluating the electron impact TICS plays a vital role in ion-beam radiobiology simulation at the cellular level, as secondary electrons are the main cause of DNA damage in particle cancer therapy. Our method is based on extending the dielectric formalism. The calculated results agree well with experimental data and show a good comparison with other theoretical calculations...
March 2018: Physical Review. E
https://www.readbyqxmd.com/read/29775571/effect-of-methylglyoxal-on-reactive-oxygen-species-ki-67-and-caspase-3-expression-in-mcf-7-cells
#20
Dyah Paramita, J D P Wisnubroto
BACKGROUND: Methylglyoxal (MG) is an extremely reactive α-ketoaldehyde endogenously produced by various metabolic pathways, including the dephosphorylation of glycolytic intermediates, metabolites of the polyol pathway, and aminoacetone metabolism. MG cytotoxicity occurs through the induction of apoptosis. There are multiple mechanisms by which MG can induce apoptosis, e.g., through the generation of reactive oxygen species (ROS), induction of oxidative DNA damage, or accumulation of a specific MG-derived advanced glycation end product (AGE)...
May 15, 2018: Experimental and Molecular Pathology
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