Search results for "Repair"
showing 10 items of 747 documents
Messing Up the Cancer Stem Cell Chemoresistance Mechanisms Supported by Tumor Microenvironment
2021
Despite the recent advances in cancer patient management and in the development of targeted therapies, systemic chemotherapy is currently used as a first-line treatment for many cancer types. After an initial partial response, patients become refractory to standard therapy fostering rapid tumor progression. Compelling evidence highlights that the resistance to chemotherapeutic regimens is a peculiarity of a subpopulation of cancer cells within tumor mass, known as cancer stem cells (CSCs). This cellular compartment is endowed with tumor-initiating and metastasis formation capabilities. CSC chemoresistance is sustained by a plethora of grow factors and cytokines released by neighboring tumor…
Significance of various enzymes in the control of reactive metabolites
1987
Most chemical carcinogens are relatively inert and need metabolic activation to the ultimately carcinogenic species. The concentration of such species is controlled by several different enzymes. Especially well studied is the important group of enzymes responsible for the control of reactive epoxides. Many natural, as well as man-made foreign compounds, including pharmaceuticals, possess olefinic or aromatic double bonds. Such compounds can be transformed to epoxides by microsomal monooxygenases present in many mammalian organs. By virtue of their electrophilic reactivity, such epoxides may spontaneously react with nucleophilic centres in the cell and thus covalently bind to DNA, RNA and pr…
RNase H1 and H2 are differentially regulated to eliminate RNA-DNA hybrids
2019
SUMMARYRNA-DNA hybrids are tightly regulated to ensure genome integrity. The RNase H enzymes, RNase H1 and H2, contribute to chromosomal stability through the removal of RNA-DNA hybrids. Loss of RNase H2 function is implicated in human diseases of the nervous system and cancer. To better understand RNA-DNA hybrid dynamics, we have focused on elucidating the regulation of the RNase H enzymes themselves. Using yeast as a model system, we demonstrate that RNase H1 and H2 are controlled in different manners. RNase H2 is regulated in a strict cell cycle dependent manner, both in terms of its R-loop removal, and ribonucleotide excision repair functions. RNase H1, however, can function independent…
Determination of steady-state levels of oxidative DNA base modifications in mammalian cells by means of repair endonucleases
1997
The alkaline elution technique in combination with various repair endonucleases (Fpg protein, endonuclease III, exonuclease III, T4 endonuclease V) was used to quantify steady-state (background) levels of oxidative base modifications in various types of mammalian cells. In human lymphocytes the number of base modifications sensitive to Fpg protein, which include 8-hydroxyguanine, was 0.25 +/- 0.05 per 10(6) base pairs. Even lower levels (0.07 +/- 0.02 per 10(6) bp) were observed in HeLa cells. The numbers of sites sensitive to the other repair endonucleases were below the detection limit (0.05 per 10(6) bp). In a direct comparison, the background level of Fpg-sensitive modifications determi…
Injectable in situ forming hydrogels based on natural and synthetic polymers for potential application in cartilage repair
2015
In this work we prepared two new hyaluronic acid (HA) based in situ forming hydrogels for the potential treatment of articular cartilage damages. In particular the amino derivative of HA (HA-EDA) and its graft copolymer with α-elastin (HA-EDA-g-α-elastin) were crosslinked, in mild physiological conditions via Michael-type addition, with α,β-poly(N-2-hydroxyethyl)-dl-aspartamide (PHEA) derivatized with divinylsulfone (DV). The swelling and degradation profile of the obtained hydrogels as well as the metabolic activity of incorporated bovine articular chondrocytes were investigated. Histological analysis and scanning electron microscopy (SEM) were performed to analyze the morphology of cells …
Individual Differences in DNA Repair Capacities in Man
1987
After metabolic activation of benzo[a]pyrene to the 7,8-dihydrodiol- 9,10-epoxide, this ultimate carcinogen preferentially binds to the exocyclic amino group of guanine. In order to investigate possible interindividual differenes in the capacity of repair of the DNA adducts formed from benzo[a]- pyrene 7,8-dihydrodiol 9,10-epoxide, their persistence in freshly isolated lymphocytes of several donors was studied. The results show a surprisingly large interindividual variation in DNA adduct formation and their persistence in freshly isolated lymphocytes. This range included several individuals with an apparent complete lack of repair capability for these adducts. Compared with controls, smoker…
Oxidative DNA Damage Profiles in Mammalian Cells
1997
Reactive oxygen species (ROS) are formed inside cells not only under the influence of exogenous agents (visible light, ionizing radiation, and many oxidants such as peroxides or quinones), but also under normal (physiological) conditions as byproducts of oxygen metabolism and other cellular redox reactions (Pryor 1986; Halliwell and Gutteridge 1986; Sies 1986; Clayson et al. 1994). ROS such as hydroxyl radicals and singlet oxygen are a serious threat to the integrity of the cellular genome, since they efficiently react with DNA to generate many types of DNA modifications, at least some of which are pre- mutagenic (Breimer 1990; Halliwell and Aruoma 1991; Epe 1991; Feig et al. 1994). Steady-…
Interaction of antimutagenic 1,4-dihydropyridine AV-153-Na with DNA and DNA-damaging molecules and its impact on DNA repair activity
2017
1,4-dihydropyridines (1,4-DHP) possess important biochemical and pharmacological properties, including antioxidant and antimutagenic activities. Interaction of some 1,4-DHP with DNA was recently reported. AV-153-Na, an antimutagenic and DNA-repair-enhancing compound appeared to be able to interact with DNA by intercalation. The aim of the current study was to characterize DNA’s capacity for the binding of AV-153-Na, and using different approaches, to test intracellular distribution of the compound, to test the ability of the compound to scavenge peroxynitrite and hydroxyl radical and to assess the ability of the compound to modify the activity of DNA repair enzymes. The DNA binding activity…
Role of Nitric Oxide for Modulation of Cancer Therapy Resistance
2010
Reactive nitrogen species (RNS) act as central second messengers in a balanced cellular network. While the complexity of nitric oxide (NO) signaling is far from being understood, and many controversial data can be found in the literature, there is evidence for NO as a major player of modulation of resistance to anticancer drugs and radiotherapy. Hypoxia in cancer tissues causes therapy resistance, and the hypoxia-inducing factor-1 (HIF-1) plays a predominant role in hypoxia-induced resistance. NO and NO-donating compounds sensitize tumor cells by inhibiting HIF-1 mediated transcription in hypoxic cells. Among a plethora of other genes, HIF-1-induced the transcription of the multidrug resist…
Induction of DNA Repair Genes in Mammalian Cells in Response to Genotoxic Stress
2006
Genotoxic agents provoke the activation of receptor-triggered pathways and DNA damage-related functions. Here we review data on immediate-early cellular responses and transcriptional activation of DNA repair genes following exposure of mammalian cells to genotoxic stress. Functional consequences of induction of DNA repair genes are also briefly discussed.