Search results for: DNA DAMAGE
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Early models of DNA damage formation
PublicationPrzeanalizowano jedne z pierwszych modeli opisujących uszkodzenia nici DNA. Przeanalizowano uszkodzenia powstające w pojedynczych i podwójnych niciach, pod wpływem czynników fizycznych i chemicznych.
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Oxidative stress in humans: validation of biomarkers of DNA damage
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Total DNA Methylation Changes Reflect Random Oxidative DNA Damage in Gliomas
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Total DNA methylation as a biomarker of DNA damage and tumor malignancy in intracranial meningiomas
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Teloxantron inhibits the processivity of telomerase with preferential DNA damage on telomeres
PublicationTelomerase reactivation is one of the hallmarks of cancer, which plays an important role in cellular immortalization and the development and progression of the tumor. Chemical telomerase inhibitors have been shown to trigger replicative senescence and apoptotic cell death both in vitro and in vivo. Due to its upregulation in various cancers, telomerase is considered a potential target in cancer therapy. In this study, we identified...
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Effects of basal level of antioxidants on oxidative DNA damage in humans
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Oxidative DNA Damage in Blood of CVD Patients Taking Detralex
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H2AX phosphorylation, its role in DNA damage response and cancer therapy
PublicationDouble-strand breaks (DSBs) are the most deleterious DNA lesions, which, if left unrepaired, may have severe consequences for cell survival, as they lead to chromosome aberrations, genomic instability, or cell death. Various physical, chemical, and biological factors are involved in DSB induction. Cells respond to DNA damage by activating the so-called DNA damage response (DDR), a complex molecular mechanism developed to detect...
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Cellular senescence induced by DNA damage and its role in carcinogenesis and chemotherapy
PublicationUszkodzenia DNA indukują w komórce różne procesy, w tym starzenie komórkowe, co może uruchamiać proces karcinogenezy jak i być związane z odpowiedzią na leki przecinowotworowe. Biologiczna rola starzenia komórkowego nie jest jednak jasna. Zasugerowano, że proces starzenia komórkowego może hamować proces karcinogenezy poprzez indukcję nieodwracalnego zahamowania wzrostu przez czynniki genotoksyczne. Indukcja starzenia komórkowego...
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Oxidative DNA damage in cancer patients: a cause or a consequence of the disease development?
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Selenium Supplementation Reduced Oxidative DNA Damage in Adnexectomized BRCA1 Mutations Carriers
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Comparison of Oxidative Stress/DNA Damage in Semen and Blood of Fertile and Infertile Men
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Dominant Pathways of Adenosyl Radical-Induced DNA Damage Revealed by QM/MM Metadynamics
PublicationBrominated nucleobases sensitize double stranded DNA to hydrated electrons, one of the dominant genotoxic species produced in hypoxic cancer cells during radiotherapy. Such radiosensitizers can therefore be administered locally to enhance treatment efficiency within the solid tumor while protecting the neighboring tissue. When a solvated electron attaches to 8-bromoadenosine, a potential sensitizer, the dissociation of bromide...
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Melatonin as a major skin protectant: from free radical scavenging to DNA damage repair
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Oxidative stress and oxidative DNA damage is characteristic for mixed Alzheimer disease/vascular dementia
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Cellular Turnover: A Potential Metabolic Rate–Driven Mechanism to Mitigate Accumulation of DNA Damage
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Oxidative DNA damage: assessment of the role in carcinogenesis, atherosclerosis, and acquired immunodeficiency syndrome1 1This article is part of a series of reviews on “Oxidative DNA Damage and Repair.” The full list of papers may be found on the homepage of the journal.
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Gentiana asclepiadea exerts antioxidant activity and enhances DNA repair of hydrogen peroxide- and silver nanoparticles-induced DNA damage
PublicationExposure to high levels of different environmental pollutants is known to be associated with induction of DNA damage in humans. Thus DNA repair is of great importance in preventing mutations and contributes crucially to the prevention of cancer. In our study we have focused on quantitative analysis of Gentiana asclepiadea aqueous or methanolic extracts obtained from flower and haulm, their antioxidant potency in ABTS post-column...
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Influence of Polymorphisms in DNA Repair GenesXPD, XRCC1andMGMTon DNA Damage Induced by Gamma Radiation and its Repair in LymphocytesIn Vitro
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Molecular basis for the DNA damage induction and anticancer activity of asymmetrically substituted anthrapyridazone PDZ-7
Publicationnthrapyridazones, imino analogues of anthraquinone, constitute a family of compounds with remarkable anti-cancer activity. To date, over 20 derivatives were studied, of which most displayed nanomolar cytotoxicity towards broad spectrum of cancer cells, including breast, prostate and leukemic ones. BS-154, the most potent derivative, had IC50 values close to 1 nM, however, it was toxic in animal studies. Here, we characterize another...
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Prolonged Quercetin Administration Diminishes the Etoposide-Induced DNA Damage in Bone Marrow Cells of Rats
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Effects of Salvia officinalis and Thymus vulgaris on oxidant-induced DNA damage and antioxidant status in HepG2 cells
PublicationSalvia officinalis (SO) and Thymus vulgaris (TV) are medicinal plants well known for their curative powers. However, the molecular mechanisms responsible for these abilities of sage and thyme have not been fully understood yet. In this study we investigated the composition and the quantitative estimation of plant extracts, the protective effects of plant extracts against hydrogen peroxide- and 2,3-dimethoxy-1,4 naphthoquinone-induced...
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Functional Interfaces, Biological Pathways, and Regulations of Interferon-Related DNA Damage Resistance Signature (IRDS) Genes
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Comparison of antioxidant enzyme activities and DNA damage in chickpea (Cicer arietinum L.) genotypes exposed to vanadium
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Cross-talk between DNA damage and cell survival checkpoints during G2 and mitosis: pharmacological implications
PublicationW pracy wyjaśnialiśmy rolę surwiwiny w ochronie komórek w czasie przejścia między G2 i mitozą, traktowanych związkiem uszkadzającym DNA. Jako model komórkowy wybraliśmy komórki ludzkiej białaczki MOLT-4, które wykazują zwiększoną ekspresję białka surwiwiny i niefunkcjonalnym p53. Ekspozycja tych komórek na melfalan, klasyczny związek uszkadzający DNA, prowadzi do uruchomienia punktu kontrolnego w G2 i zablokowania progresji cyklu...
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Mechanism of selective anticancer activity of isothiocyanates relies on differences in DNA damage repair between cancer and healthy cells
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Oxidative DNA damage and antioxidant vitamin level: Comparison among lung cancer patients, healthy smokers and nonsmokers
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Viral infection-oxidative stress/DNA damage-aberrant DNA methylation: separate or interrelated events responsible for genetic instability and childhood ALL development?
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Fine-tuning recA expression in Staphylococcus aureus for antimicrobial photoinactivation: importance of photo-induced DNA damage in the photoinactivation mechanism
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Berry fruit juices protect lymphocytes against DNA damage and ROS formation induced with heterocyclic aromatic amine PhIP
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Relationships between acute reactions to radiotherapy in head and neck cancer patients and parameters of radiation-induced DNA damage and repair in their lymphocytes
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Dual inhibition of PI3K/Akt signaling and the DNA damage checkpoint in p53-deficient cells with strong survival signaling: implications for cancer therapy
PublicationOporność komórek nowotworowych na leki uszkadzjące DNA związana jest ściśle ze zdolnością do utrzymywania blok z fazie G2 cyklu komórkowego. Blok ten regulowany jest przez mechanizmy punktu kontrolnego G2/M oraz szlaki przeżycia komórkowego. W pracy badaliśmy rolę szlaku kinazy PI3K/Akt w funkcjonowaniu punktu kontrolnego cyklu komórkowego i wpływ na przeżycie komórek traktowanych lekiem przeciwnowotworowym - cisplatyną. Nasze...
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The changes of antioxidant defense system caused by quercetin administration do not lead to DNA damage and apoptosis in the spleen and bone marrow cells of rats
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Combination of ABT-737 and resveratrol enhances DNA damage and apoptosis in human T-cell acute lymphoblastic leukemia MOLT-4 cells
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Gene expression, DNA damage and other stress markers in Sinapis alba L. exposed to heavy metals with special reference to sewage sludge application on contaminated sites
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Mechanism for Damage to DNA by Low-Energy Electrons
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Evaluating experimental molecular physics studies of radiation damage in DNA*
PublicationThe field of Atomic and Molecular Physics (AMP) is a mature field exploring the spectroscopy, excitation, ionisation of atoms and molecules in all three phases. Understanding of the spectroscopy and collisional dynamics of AMP has been fundamental to the development and application of quantum mechanics and is applied across a broad range of disparate disciplines including atmospheric sciences, astrochemistry, combustion and environmental...
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Effects of Base π-Stacking on Damage to DNA by Low-Energy Electrons
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Mechanisms of Damage to DNA Labeled with Electrophilic Nucleobases Induced by Ionizing or UV Radiation
PublicationHypoxia—a hallmark of solid tumors—makes hypoxic cells radioresistant. On the other hand, DNA, the main target of anticancer therapy, is not sensitive to the near UV photons and hydrated electrons, one of the major products of water radiolysis under hypoxic conditions. A possible way to overcome these obstacles to the efficient radio- and photodynamic therapy of cancer is to sensitize the cellular DNA to electrons and/or ultraviolet...
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Theoretical Study of Damage to DNA by 0.2−1.5 eV Electrons Attached to Cytosine
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Damage to Model DNA Fragments from Very Low-Energy (<1 eV) Electrons
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Urinary Measurement of 8-OxodG, 8-OxoGua, and 5HMUra: A Noninvasive Assessment of Oxidative Damage to DNA
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The Protective Effect of Dabigatran and Rivaroxaban on DNA Oxidative Changes in a Model of Vascular Endothelial Damage with Oxidized Cholesterol
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The protective effect of dabigatran and rivaroxaban on DNA oxidative changes in a model of vascular endothelial damage with oxidized cholesterol
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Modelling charge transfer processes in C2+ -tetrahydrofuran collision for ion-induced radiation damage in DNA building blocks
PublicationInvestigations of collision-induced processes involving carbon ions and molecules of biological interest in particular DNA building blocks, are crucial to model the effect of radiation on cells in order to improve medical treatments for cancer therapy. Using carbon ions appears to be one of the most efficient ways to increase biological effectiveness to damage cancerous cells by irradiating deep-seated tumors. Therefore, interest...
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From DNA damage to G2 arrest: the many roles of topoisomerase II. W: Prog-ress in Cell Cycle Research. Ed. Meijer L., Jezequel A., Roberge M. London: Plenum Publ. Comp. Ltd**2003 vol. 5 chapt. 30 s. 295-300 Od uszkodzeń DNA do bloku w G2: wiele ról dla topoizomerazy II.
PublicationInhibitory DNA topoizomerazy II sa jednymi z najbardziej szeroko stosowanymi lekami przeciwnowotworowymi. Związki te indukuja pekniecia nici DNA i bloku progresji cyklu komorkowego w fazie G2. Jednak topoizomeraza II jest nie tylko celem molekularnym dla lekow przeciwnowtworowych ale enzym ten pelniwazna role w odpowiedzi komorkowej na dzialanie wielu lekow uszkadzajacych DNA. Topoizomeraza tworzy kompleksy molekularne z bialkami...
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Intramolecular Proton Transfer in the Radical Anion of Cytidine Monophosphate Sheds Light on the Sensitivities of Dry vs Wet DNA to Electron Attachment-Induced Damage
PublicationSingle-strand breaks (SSBs) induced via electron attachment were previously observed in dry DNA under ultrahigh vacuum (UHV), while hydrated electrons were found not able to induce this DNA damage in an aqueous solution. To explain these findings, crossed electron-molecular beam (CEMB) and anion photoelectron spectroscopy (aPES) experiments coupled to density functional theory (DFT) modeling were used to demonstrate the fundamental...
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Generation and Characterization of a DNA-GCN4 Oligonucleotide-Peptide Conjugate: The Impact DNA/Protein Interactions on the Sensitization of DNA
PublicationRadiotherapy, the most common therapy for the treatment of solid tumors, exerts its effects by inducing DNA damage. To fully understand the extent and nature of this damage, DNA models that mimic the in vivo situation should be utilized. In a cellular context, genomic DNA constantly interacts with proteins and these interactions could influence both the primary radical processes (triggered by ionizing radiation) and secondary reactions,...
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VUV irradiation studies of plasmid DNA in aqueous solution
PublicationInteractions of VUV light and DNA samples in aqueous solutions are reported. The damage induced by such radiation is quantified by monitoring both loss of supercoiled DNA and formation of single and double strand breaks using agarose gel electrophoresis. Irradiations were performed using synchrotron VUV photons of 130, 150, 170 and 190 nm. VUV irradiation experiments revealed enhanced damage upon irradiation with 170 nm photons...
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X-ray and UV Radiation Damage of dsDNA/Protein Complexes
PublicationRadiation and photodynamic therapies are used for cancer treatment by targeting DNA. However, efficiency is limited due to physico-chemical processes and the insensitivity of native nucleobases to damage. Thus, incorporation of radio- and photosensitizers into these therapies should increase both efficacy and the yield of DNA damage. To date, studies of sensitization processes have been performed on simple model systems, e.g.,...
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Preparation of DNA films for studies under vacuum conditions
PublicationExperiments were carried out to determine the optimum conditions required for the preparation of uniform films of supercoiled plasmid DNA to be used in irradiation experiments under high vacuum conditions. Investigations reveal that significant damage to the DNA molecules occurs due to the evacuation process when films were formed from DNA samples in ultra high purity water only. A variety of bases were tested for their possible...
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Silver nanoparticles induce premutagenic DNA oxidation that can be prevented by phytochemicals from Gentiana asclepiadea
PublicationAmong nanomaterials, silver nanoparticles (AgNPs) have the broadest and most commercial applications due to their antibacterial properties, highlighting the need for exploring their potential toxicity and underlying mechanisms of action. Our main aim was to investigate whether AgNPs exert toxicity by inducing oxidative damage to DNA in human kidney HEK 293 cells. In addition, we tested whether this damage could be counteracted...
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Hydroperoxyl radical and formic acid formation from common DNA stabilizers upon low energy electron attachment
Publication2-Amino-2-(hydroxymethyl)-1,3-propanediol (TRIS) and ethylenediaminetetraacetic acid (EDTA) are key components of biological buffers and are frequently used as DNA stabilizers in irradiation studies. Such surface or liquid phase studies are done with the aim to understand the fundamental mechanisms of DNA radiation damage and to improve cancer radiotherapy. When ionizing radiation is used, abundant secondary electrons are formed...
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Telomere uncapping by common oxidative guanine lesions: Insights from atomistic models
PublicationOxidative damage to DNA is widely known to contribute to aging and disease. This relationship has been extensively studied for telomeres – structures that cap chromosome ends – due to their role in cell proliferation and senescence, and exceptional susceptibility to oxidation. Indeed, the repetitive telomeric DNA sequence contains the 5′-GGG-3′ motif that has the lowest ionization potential of all trinucleotides. Accordingly, experiments...
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Radio- and photosensitization of DNA with compounds containing platinum and bromine atoms
Publication. Irradiations of plasmid DNA by both X-rays and UV light in the presence and absence of compounds containing platinum and bromine atoms were performed in order to asses the sensitization potential of these compounds. Plasmid DNA pBR322 was incubated with platinum (II) bromide, hydrogen hexabromoplatinate (IV), hydrogen hexahydroxyplatinate (IV) and sodium hexahydroxyplatinate (IV). Incubation was followed by X-ray or UV irradiations....
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The extended version of restriction analysis approach for the examination of the ability of low-molecular-weight compounds to modify DNA in a cell-free system
PublicationOne of the primary requirements in toxicology is the assessment of ability of chemicals to induce DNA covalent modification. There are several well-established methods used for this purpose such as 32P-Postlabeling or HPLC-MS. However, all of these approaches have difficult to overcome limitations, which prevents their use in genotoxin screening. Here, we describe the simple protocol exploiting specificity of restriction enzymes...
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DNA methylation in cancer development, diagnosis and therapy-multiple opportunities for genotoxic agents to act as methylome disruptors or remediators
PublicationThe role of DNA methylation and recently discovered hydroxymethylation in the function of the human epigenome is currently one of the hottest topics in the life sciences. Progress in this field of research has been further accelerated by the discovery that alterations in the methylome are not only associated with key functions of cells and organisms, such as development, differentiation and gene expression, but may underlie a number...
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Biochemical, Structural Analysis, and Docking Studies of Spiropyrazoline Derivatives
PublicationIn this study, we evaluated the antiproliferative potential, DNA damage, crystal struc‐ tures, and docking calculation of two spiropyrazoline derivatives. The main focus of the research was to evaluate the antiproliferative potential of synthesized compounds towards eight cancer cell lines. Compound I demonstrated promising antiproliferative properties, especially toward the HL60 cell line, for which IC50 was equal to 9.4 μM/L....
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Novel anticancer strategy aimed at targeting shelterin complexes by the induction of structural changes in telomeric DNA: hitting two birds with one stone.
PublicationThe ends of chromosomes in mammals are composed of telomeric DNA containing TTAGGG repeats, which bind specific proteins called shelterins. This telomeric DNA together with shelterins form a cap that protects the ends of chromosomes from being recognized as sites of DNA damage and from chromosomal fusions. Many very successful antitumor drugs used in the treatment of cancer patients bind to DNA, some of them with a prominent sequence...
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Changes in Epigenetic Patterns Related to DNA Replication in Vicia faba Root Meristem Cells under Cadmium-Induced Stress Conditions
PublicationExperiments on Vicia faba root meristem cells exposed to 150 µM cadmium chloride (CdCl2) were undertaken to analyse epigenetic changes, mainly with respect to DNA replication stress. Histone modifications examined by means of immunofluorescence labeling included: (1) acetylation of histone H3 on lysine 56 (H3K56Ac), involved in transcription, S phase, and response to DNA damage during DNA biosynthesis; (2) dimethylation of histone...
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Photoinduced electron transfer in 5-bromouracil labeled DNA. A contrathermodynamic mechanism revisited by electron transfer theories
PublicationThe understanding of the 5-bromouracil (BrU) based photosensitization mechanism of DNA damage is of large interest due to the potential applications in photodynamic therapy. Photoinduced electron transfer (ET) in BrU labeled duplexes comprising the 50 -GBrU or 50 -ABrU sequence showed that a much lower reactivity was found for the 50 -GBrU pattern. Since the ionization potential of G is lower than that of A, this sequence selectivity...
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Decomposition of halogenated nucleobases by surface plasmon resonance excitation of gold nanoparticles
PublicationHalogenated uracil derivatives are of great interest in modern cancer therapy, either as chemotherapeutics or radiosensitisers depending on their halogen atom. This work applies UV-Vis spectroscopy to study the radiation damage of uracil, 5-bromouracil and 5- uorouracil dissolved in water in the presence of gold nanoparticles upon irradiation with an Nd:YAG ns-pulsed laser operating at 532nm at dierent uences. Gold nanoparticles...
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Chromatographic analyses of Lavandula angustifolia and Rosmarinus officinalis extracts and their biological effects in mammalian cells and cell-free systems
PublicationKnowledge of biological properties of natural compounds allows to understand their therapeutic value, efficacy and security. We investigated: composition of Lavandula angustifolia (LA) and Rosmarinus officinalis (RO) extracts, their antioxidant capacity, cytotoxicity and genotoxicity, their DNA-protective potential against DNA damage induced in hamster V79 cells by several genotoxins or in plasmid DNA by Fe2+ ions and activity...
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H2O˙+ and OH+ reactivity versus furan: experimental low energy absolute cross sections for modeling radiation damage
PublicationRadiotherapy is one of the most widespread and efficient strategies to fight malignant tumors. Despite its broad application, the mechanisms of radiation-DNA interaction are still under investigation. Theoretical models to predict the effects of a particular delivered dose are still in their infancy due to the difficulty of simulating a real cell environment, as well as the inclusion of a large variety of secondary processes. This...
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The role of epigenetics in regeneration
PublicationComplex changes in chromatin structure and at the transcriptional level occur from the creation of a single parental gamete throughout fertilization, embryo development and the life of an adult organism. Epigenetic changes, such as methylation and hydroxymethylation of DNA or histone methylation and acetylation, are an important part of these processes. Epigenetic regulation has an essential influence on gene expression level. DNA...
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Jacek Chróścielewski prof. dr hab. inż.
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Novel fused pyran derivatives induce apoptosis and target cell cycle progression in anticancer efficacy against multiple cell lines.
PublicationNitrogen-based heterocycles such as pyrazole, imidazole, 1,2,4-triazole, benzimidazole, and benzotriazole substituted fused pyran derivatives (6a–e, 8a–e, 10a–e, 12a–e,&14a–e) have been synthesized and tested for their in vitro anticancer efficacies against MCF7, A549, and HCT116 cancer cell lines. Among the compounds, 6e, 14b, and 8c were identified as the most potent against MCF7, A549, and HCT116, with IC50 values of 12.46 2.72...
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Analysis of the influence of polystyrene microplastics and their derivatives on the DNA of human colon epithelial cells HT29 with the comet assay
PublicationWe have been using plastic for almost a century and nowadays a lot of them circulates as pollutants in the environment and still defragmenting to micro and nanoscale. The exposition through the food chain and its precise impact on human health is still not clear. In our study, we tested real food packaging after contact with food products and real thermoinsulation and environmental samples of polystyrene in different model liquids,...
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Cardinal regenerative features of the MRL mouse
PublicationIn this review, we discuss recent studies relating to major features of adult MRL mouse biology that contribute to the regenerative responses seen. These include an increased inflammatory cell profile, a unique glycolytic metabolic state typically found during embryogenesis, and a cell cycle phenotype of DNA damage and G2/M arrest. These traits have been found in other mammalian and non-mammalian regenerative systems. How these...
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Anticancer Imidazoacridinone C-1311 is Effective in Androgen-Dependent and Androgen-Independent Prostate Cancer Cells
PublicationAndrogen receptor (AR) plays a crutial role in prostate cancer (PCa) development and metastasis. Here, we reported potent anti-PCa activity of a small molecule imidazoacridinone C-1311. In AR-positive PCa cells, C-1311 was found to inhibit the transcriptional activity of AR uncovering a novel mechanism that may be relevant for its anticancer effect. Mechanistically, C-1311 decreased AR binding to prostate-specific antigen (PSA)...
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The Toolbox of Methods for Multidirectional Characterization of Dietary Nucleic Acids; Verification for Raw and Processed Food Products
PublicationCurrently, the nutritional value of food is associated mainly with components such as proteins, carbohydrates, and lipids. However, another important macromolecules present in many foods are dietary nucleic acids (dietNA), i.e., DNA as well as both coding and non-coding RNAs. In the context of food chemistry and nutrition, dietNA are nowadays vastly neglected. In consequence, there are no dedicated methodologies to characterize...
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Genotoxic properties of glucosinolates and isothiocyanates present in Brassica vegetables
PublicationThe bioactive phytochemicals found in Brassica vegetables, in this number glucosinolates (GLS), as well as products of their degradation such as isothiocyanates (ITC) and indoles, are regarded as the most promising chemopreventive compounds. These secondary metabolites display stron antibiological activity and constitute defence system preventing the development of agrophages attacking Brassica plants. Such properties suggest...
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5-Bromo-2′-deoxycytidine—a potential DNA photosensitizer
PublicationA double-stranded oligonucleotide, 80 base pairs in length, was multiply labeled with 5-bromo-2′-deoxycytidine (BrdC) using polymerase chain reaction (PCR). The modified oligonucleotide was irradiated with 300 nm photons and its damage was assayed by employing DHPLC, LC-MS and denaturing polyacrylamide gel electrophoresis (PAGE). Two types of damage were demonstrated, namely, single strand breaks (SSBs) and intrastrand cross-links...
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Sequence variants of p21 gene of the MRL/MpJ mouse: a possible association with the deficit of p21 protein and regenerative phenotype.
PublicationThe MRL/MpJ mouse is known for its enhanced regeneration abilities that manifested themselves by scarless ear-hole wound closure. The deficit of p21 found in the MRL is associated with the regenerative capacity as the p21 gene knockout in a mouse strain unrelated to the MRL mouse results in an ear-hole closure effect, similar to that observed in the MRL mouse. Cdkn1a gene encodes p21 protein, a cyclin-dependent kinase inhibitor,...
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9,10-Dioxoanthracenyldithiocarbamates effectively inhibit the proliferation of non-small cell lung cancer by targeting multiple protein tyrosine kinases
PublicationAnthraquinones have attracted considerable interest in the realm of cancer treatment owing to their potent anticancer properties. This study evaluates the potential of a series of new anthraquinone derivatives as anticancer agents for non-small-cell lung cancer (NSCLC). The compounds were subjected to a range of tests to assess their cytotoxic and apoptotic properties, ability to inhibit colony formation, pro-DNA damage functions,...
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Genotoxicity of selected pharmaceuticals, their binary mixtures, and varying environmental conditions – study with human adenocarcinoma cancer HT29 cell line
PublicationPharmaceutical residues are present in the environment in mixtures and their adverse effects may also result from interactions that occur between compounds. Studies presented in this work focus on genotoxicity of pharmaceuticals from different therapeutic groups in mixtures and in individual solutions impacted with different environmental conditions assessed using comet assay (alkaline approach). Binary mixtures of pharmaceuticals...
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Electron-Induced Decomposition of 5-Bromo-4-thiouracil and 5-Bromo-4-thio-2′-deoxyuridine: The Effect of the Deoxyribose Moiety on Dissociative Electron Attachment
PublicationWhen modified uridine derivatives are incorporated into DNA, radical species may form that cause DNA damage. This category of molecules has been proposed as radiosensitizers and is currently being researched. Here, we study electron attachment to 5-bromo-4-thiouracil (BrSU), a uracil derivative, and 5-bromo-4-thio-20 -deoxyuridine (BrSdU), with an attached deoxyribose moiety via the N-glycosidic (N1-C) bond. Quadrupole mass spectrometry...
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Electron-Induced Decomposition of Uracil-5-yl O-(N,N-dimethylsulfamate): Role of Methylation in Molecular Stability
PublicationThe incorporation of modified uracil derivatives into DNA leads to the formation of radical species that induce DNA damage. Molecules of this class have been suggested as radiosensitizers and are still under investigation. In this study, we present the results of dissociative electron attachment to uracil-5-yl O-(N,N-dimethylsulfamate) in the gas phase. We observed the formation of 10 fragment anions in the studied range of electron...
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A new division of bacterial UvrA homologues
PublicationThe UvrA protein is a DNA-binding and damage-recognition enzyme which participates in the prokaryotic type nucleotide excision repair (NER) pathway. It has recently been noted that some bacterial genomes comprise additional uvrA genes which encode five distinct types of UvrA homologue. We investigated the sequences of over 2400 bacterial genomes and found 130 examples of bacteria containing uvrA 2 genes. The sequence analyses conducted...
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The role of the sawage treatment plant in the removal of genotoxic compounds from the environment
PublicationOne reason for increased incidence of various types of cancer are environmental pollutants particularly of anthropogenic origin. All human activities may pollute the environment, but some have significant impact, just to mention energy industry, mining, transportation, chemical and petrochemical industries and housing. Environmental pollutants are a large group of compounds in terms of their physicochemical properties, some of...
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The relationship between standard reduction potentials of catechins and biological activities involved in redox control
PublicationRedox homeostasis involves factors that ensure proper function of cells. The excess reactive oxygen species (ROS) leads to oxidative stress and increased risk of oxidative damage to cellular components. In contrast, upon reductive stress, insufficient ROS abundance may result in faulty cell signalling. It may be expected that dietary antioxidants, depending on their standard reduction potentials (E°), will affect both scenarios....
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From tryptophan to novel mitochondria-disruptive agent, synthesis and biological evaluation of 1,2,3,6-tetrasubstituted carbazoles
PublicationMitochondrial targeting plays an important role in anticancer therapy. The Mn(III)-promoted cyclization of 5- (1H-indol-3-yl)-3-oxopentanoic acid allow to obtain novel substituted carbazole derivatives that can act as mitochondria-disruptive agents. The starting materials used for the synthesis of these new aminocarbazoles are oxopentanoate derivatives of tryptophan. The scope and limitation of this method of synthesis are determined...
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Cell-penetrating peptides – mechanism of transduction and synthesis – short review
PublicationPotential antimicrobial agents may be effective if they are delivered efficiently to their site of action. In many cases, lack of permeability through the cell membrane is the main problem. One of the possible solutions could be a novel intracellular delivery system involving cell-penetrating peptides (CPPs), which may improve the efficiency of many new biophar-maceuticals. Among other things, CPPs are capable of trans-porting...
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VUV photofragmentation of the six-membered heterocyclic molecules containing oxygen
PublicationCancer is a significant public health concern worldwide, which results in millions of deaths each year. The standard cure routine for cancer is surgery, and nowadays, radiotherapy or a hadrontherapy. Depending on the type of cancer, patients may undergo additional treatment, including targeted therapy. A combination of radio- or hadron-therapy with proper drug treatment can inhibit the proliferation of cancer cells and thus can...
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Dietary intervention with beetroot juice during doxorubicin cancer chemotherapy in vivo reduces markers of oxidative stress
PublicationCancer chemotherapy with doxorubicin, despite high antitumor activity and broad spectrum of this drug, is on decline due to toxic side effects. The clinical efficacy of anthracyclines have continuously prompted the search for new adjuvants to alleviate undesirable side toxicity incurred by this group of cytostatics. The recent approaches involve the application of synthetic or purified natural antioxidants in combination with doxorubicin...
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The comparison of cytotoxic and genotoxic activities of glucosinolates, isothiocyanates, and indoles
PublicationChemopreventive properties of Brassica vegetables are attributed mainly to their characteristic compounds—glucosinolates (GLs) and their main hydrolysis products—isothiocyanates (ITCs) and indoles. In this study, we compared antiproliferative activity (MTT test in HT29 cells) and genotoxic effects (comet assay in HT29 cells and restriction analysis in a cell-free system) of three GLs (sinigrin (SIN), glucotropaeolin (GTL), and...
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Paweł Możejko dr hab.
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The influence of global climate change on the environmental fate of anthropogenic pollution released from the permafrost
PublicationThis article presents a review of information related to the influence of potential permafrost degradation on the environmental fate of chemical species which are relased and stored, classified as potential influence in future Antarctic environment. Considering all data regarding climate change prediction, this topic may prove important issue for the future state of the Antarctic environment. A detailed survey on soil and permafrost...
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The influence of sterilization with EnbioJet Microwave Flow Pasteurizer on composition and bioactivity of aronia and blue-berried honeysuckle juices
PublicationIn this study, fruit juices that are rich sources of anthocyanins, obtained from aronia (Am. chokeberry, Aronia melanocarpa) and blueberry honeysuckle (Lonicera caerulea L. var. edulis) were used to examine the preservation of plant phytochemicals and bioactivity upon sterilization -either thermal, or with an EnbioJet microwave flow pasteurizer. The chemical properties verified included determinations of anthocyanins and other...
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Synthesis of eosin modified TiO2 film with co-exposed {001} and {101} facets for photocatalytic degradation of para-aminobenzoic acid and solar H2 production
PublicationOwing to the increasing photosensitivity and DNA damage properties of para-aminobenzoic acid (PABA), concerns have been raised over the exposure of humans to PABA. Solar light-driven photocatalysis (SPC) provides a promising solution for the effective removal of organic pollutants especially when directed towards sulfate radical (SO4−) production. Herein, we have developed a sulfite-enhanced SPC using Eosin-Y sensitized TiO2/Ti...
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Dimeric structure of the N-terminal domain of PriB protein from Thermoanaerobacter tengcongensis solved ab initio
PublicationPriB is one of the components of the bacterial primosome, which catalyzes the reactivation of stalled replication forks at sites of DNA damage. The N-terminal domain of the PriB protein from the thermophilic bacterium Thermoanaerobacter tengcongensis (TtePriB) was expressed and its crystal structure was solved at the atomic resolution of 1.09 Å by direct methods. The protein chain, which encompasses the first 104 residues of the...
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Relationship between Chemical Structure and Biological Activity Evaluated In Vitro for Six Anthocyanidins Most Commonly Occurring in Edible Plants
PublicationNumerous studies have provided evidence that diets rich in anthocyanins show a broad spectrum of health benefits. Anthocyanins in nature are usually found in the form of glycosides. Their aglycone forms are called anthocyanidins. The chemical structure of anthocyanins is based on the flavylium cation, but they differ in the position and number of substituents. However, the bioactives and foods that contain them are frequently treated...
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Caffeine Inhibits Differentiation Of Lung Cancer Stem Cells By Modulating Their Respiratory Metabolism
PublicationIt is ell established that many tumor types contain a fraction of cells, with stem cell-like properties, called cancer stem cells (CSCs), that are resistant to apoptosis induced by therapeutic agents. The presence of CSCs may explain why a standard anticancer treatment, that eliminates only differentiated cancer cells, does not lead to cancer cure.We previously showed the existence of caffeine-sensitive mechanism that controls...
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Analysis of induction of DNA DSBs on telomeres in A549 cells
Open Research DataData consist of an analysis of DNA DSBs on telomeres. A549 were treated with compounds (TXT4, MTX, DMSO) at IC90 concentration for the indicated time. Images were acquired with an LSM 800 inverted laser scanning confocal microscope (Carl Zeiss; Dresden, Germany) equipped with an Airyscan detector using a ×63 1.4 NA Plan Apochromat objective (Carl Zeiss)....
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Flow cytometry analysis of DNA DSBs in telomerase positive and negative cell lines after treatment with TXT2 and TXT4
Open Research DataFlow cytometry analysis of DNA DSBs in telomerase positive (A549, H460) and negative (NHBE2594, U2OS) cell lines after treatment with equitoxic concentrations of TXT2 and TXT4. MTX and DMSO were used as positive and negative controls, respectively.
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Confocal microscopy analysis of DNA DSB in telomerase negative cells after exposure to TXT2 and TXT4
Open Research DataThe data sets contain confocal microscopic images showing the γ-H2AX with TRF2 after treatment of NHBE and U2OS cell lines with TXT2 and TXT4 in equitoxic concentrations. Images were acquired with an LSM 800 inverted laser scanning confocal microscope (Carl Zeiss; Dresden, Germany) equipped with an Airyscan detector using a ×63 1.4 NA Plan Apochromat...
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UV-induced electron transfer between triethylamine and 5-bromo-2′-deoxyuridine. A puzzle concerning the photochemical debromination of labeled DNA
Publication5-Bromo-2'-deoxyuridine (BrdU) photosensitizes DNA to strand break formation. However, this type of photodamage is completely quenched by the presence of triethylamine (TEA) which originates from RP-HPLC purification commonly employed by oligonucleotide providers. While the presence of TEA in oligonucleotide samples does not interfere with PCR or other molecular biology applications, the mechanism of photochemical reaction proceeding...
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5-Thiocyanato-2′-deoxyuridine as a possible radiosensitizer: electron-induced formation of uracil-C5-thiyl radical and its dimerization
PublicationIn this work, we have synthesized 5-thiocyanato-2′-deoxyuridine (SCNdU) along with the C6-deuterated nucleobase 5-thiocyanatouracil (6-D-SCNU) and studied their reactions with radiation-produced electrons. ESR spectra in γ-irradiated nitrogen-saturated frozen homogeneous solutions (7.5 M LiCl in H2O or D2O) of these compounds show that electron-induced S–CN bond cleavage occurs to form a thiyl radical (dU-5-S˙ or 6-D-U-5-S˙) and...
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Recombinant !ermostable AP Exonuclease from Thermoanaerobacter tengcongensis: Cloning, Expression, Purification, Properties and PCR Application
PublicationApurinic/apyrimidinic (AP) sites in DNA are considered to be highly mutagenic and must be corrected to preserve genetic integrity, especially at high temperatures. !e gene encoding a homologue of AP exonuclease was cloned from the thermophilic anaerobic bacterium Thermoanaerobacter tengcongensis and transformed into Escherichia coli. The protein product showed high identity (80%) to human Ape1 nuclease, whereas to E. coli exonuclease...
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Charge Transfer, Complexes Formation and Furan Fragmentation Induced by Collisions with Low-Energy Helium Cations
PublicationThe present work focuses on unraveling the collisional processes leading to the fragmentation of the gas-phase furan molecules under the He+ and He2+ cations impact in the energy range 5–2000 eV. The presence of different mechanisms was identified by the analysis of the optical fragmentation spectra measured using the collision-induced emission spectroscopy (CIES) in conjunction with the ab initio calculations. The measurements of...