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DNA repair inhibitors as radiosensitizers in human lung cells

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F18%3A43889304" target="_blank" >RIV/60162694:G44__/18:43889304 - isvavai.cz</a>

  • Alternative codes found

    RIV/00179906:_____/18:10369717

  • Result on the web

    <a href="https://www.sciencedirect.com/science/article/pii/S1214021X16303416" target="_blank" >https://www.sciencedirect.com/science/article/pii/S1214021X16303416</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1016/j.jab.2017.10.008" target="_blank" >10.1016/j.jab.2017.10.008</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    DNA repair inhibitors as radiosensitizers in human lung cells

  • Original language description

    The aim of this study was to compare the effects of DNA repair inhibitors in the context of radio-sensitization of human lung cells. The radio-sensitizing effects of NU7441 (1 mM), an inhibitor of DNA-dependent protein kinase (DNA-PK); KU55933 (10 μM), an inhibitor of ataxia-telangiectasia mutated kinase (ATM); and VE-821 (10 μM), an inhibitor of ATM-related kinase (ATR) were tested by the xCELLigence system for monitoring proliferation, fluorescence microscopy for DNA damage detection, flow-cytometry for cell cycle and apoptosis analysis and western blotting and ELISA for determination of DNA repair proteins. We employed normal human lung fibroblasts (NHLF, p53-wild-type) and non-small cell lung cancer cells (H1299, p53-negative). DNA-PK inhibition (by NU7441) in combination with ionizing radiation (IR) increased the number of double strand breaks (DSB), which persisted 72 h after irradiation in both cell lines. Additionally, NU7441 and KU55933 in combination with IR caused G2-arrest. ATR inhibitor (VE-821) together with IR markedly inhibited proliferation and induced G2/M arrest accompanied by apoptosis in H1299, but not in NHLF cells, and thus diminished DNA-repair of tumour cells but not normal lung fibroblasts. Our findings indicate that ATR inhibition could be a promising therapeutic strategy in p53-deficient lung tumours

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    30104 - Pharmacology and pharmacy

Result continuities

  • Project

  • Continuities

    S - Specificky vyzkum na vysokych skolach

Others

  • Publication year

    2018

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Journal of Applied Biomedicine

  • ISSN

    1214-021X

  • e-ISSN

  • Volume of the periodical

    16

  • Issue of the periodical within the volume

    1

  • Country of publishing house

    CZ - CZECH REPUBLIC

  • Number of pages

    9

  • Pages from-to

    66-74

  • UT code for WoS article

    000423027000011

  • EID of the result in the Scopus database

    2-s2.0-85034989096