Search results for "DNA Damage"

DNA folds threaten genetic stability and can be leveraged for chemotherapy

2020

International audience; Damaging DNA is a current and efficient strategy to fight against cancer cell proliferation. Numerous mechanisms exist to counteract DNA damage, collectively referred to as the DNA damage response (DDR) and which are commonly dysregulated in cancer cells. Precise knowledge of these mechanisms is necessary to optimise chemotherapeutic DNA targeting. New research on DDR has uncovered a series of promising therapeutic targets, proteins and nucleic acids, with application notably via an approach referred to as combination therapy or combinatorial synthetic lethality. In this review, we summarise the cornerstone discoveries which gave way to the DNA being considered as an…

Flipping of alkylated DNA damage bridges base and nucleotide excision repair

2009

Alkyltransferase-like proteins (ATLs) share functional motifs with the cancer chemotherapy target O6-alkylguanine-DNA alkyltransferase (AGT) and paradoxically protect cells from the biological effects of DNA alkylation damage, despite lacking the reactive cysteine and alkyltransferase activity of AGT. Here we determine Schizosaccharomyces pombe ATL structures without and with damaged DNA containing the endogenous lesion O6-methylguanine or cigarette-smoke-derived O6-4-(3-pyridyl)-4-oxobutylguanine. These results reveal non-enzymatic DNA nucleotide flipping plus increased DNA distortion and binding pocket size compared to AGT. Our analysis of lesion-binding site conservation identifies new A…

2015

Head and neck squamous cell cancer (HNSCC) is the 7th most common cancer worldwide. Despite the development of new therapeutic agents such as monoclonal antibodies, prognosis did not change for the last decades. Cold atmospheric plasma (CAP) presents the most promising new technology in cancer treatment. In this study the efficacy of a surface micro discharging (SMD) plasma device against two head and neck cancer cell lines was proved. Effects on the cell viability, DNA fragmentation and apoptosis induction were evaluated with the MTT assay, alkaline microgel electrophoresis (comet assay) and Annexin-V/PI staining. MTT assay revealed that the CAP treatment markedly decreases the cell viabil…

Metabolic detoxification: implications for thresholds.

2000

The fact that chemical carcinogenesis involves single, isolated, essentially irreversible molecular events as discrete steps, several of which must occur in a row to finally culminate in the development of a malignancy, rather suggests that an absolute threshold for chemical carcinogens may not exist. However, practical thresholds may exist due to saturable pathways involved in the metabolic processing, especially in the metabolic inactivation, of such compounds. An important example for such a pathway is the enzymatic hydrolysis of epoxides via epoxide hydrolases, a group of enzymes for which the catalytic mechanism has recently been established. These enzymes convert their substrates via…

Early ROS-mediated DNA damage and oxidative stress biomarkers in Monoclonal B Lymphocytosis

2012

Monoclonal B Lymphocytosis (MBL) is defined as asymptomatic monoclonal B-cell expansion characterised by a CLL-phenotype, but with less than 5 x 10(9)/I circulating cells. Reactive oxygen species (ROS)-mediated cell damage plays a critical role in the initiation of carcinogenesis as well as in malignant transformation. The goal of this study was to perform an analysis of the oxidative stress statuses of patients affected by MBL and chronic lymphocytic leukaemia (CLL). We examined peripheral blood and urine specimens from 29 patients with MBL, 55 with CLL and 31 healthy subjects. There was a significant increase in the occurrence of the mutagenic base 8-oxo-2'-deoxiguanosine (8-oxo-dG) in th…

Chemical Composition of Thymus leucotrichus var. creticus Essential Oil and Its Protective Effects on Both Damage and Oxidative Stress in Leptodictyu…

2022

The chemical profile of the essential oil (EO) of the aerial parts of Thymus leucotrichus var. creticus (Lamiaceae), a taxon not previously studied, was investigated by GC–MS analysis, using a DB–Wax polar column. Oxygenated monoterpenes and monoterpene hydrocarbons dominate the EO, with thymol (46.97%) and p-cymene (28.64%) as the main constituent of these two classes, respectively. The ability of the EO of T. leucotrichus to reduce Cd toxicity was studied in aquatic moss Leptodictyum riparium. To study EO-induced tolerance to Cd toxicity, apex growth, number of dead cells, DNA damage and antioxidant response in gametophytes were examined. The exogenous application of the EO yields a resum…

Abstract 857: Metal oxide nanoparticles as adjuvant for radiation therapy

2018

Abstract Background: Radiation therapy comprises a fundamental component of modern tumor treatment. Unfortunately, its success is limited by the development of radiation resistances. The emerging field of nanotechnology offers great opportunities for diagnosing, imaging, as well as treating cancer. Metal oxide nanoparticles in particular zinc oxide nanoparticles (ZnO-NP) have been shown to display a selective cytotoxic effect on tumor cells via a yet unknown mechanism. Most likely the generation of reactive oxygen species (ROS), breakdown of mitochondria and DNA damage are involved. The success of radiation therapy equally relies on the generation of ROS, which develop their cytotoxic poten…

Dual targeting of higher-order DNA structures by azacryptands induces DNA junction-mediated DNA damage in cancer cells

2021

Abstract DNA is intrinsically dynamic and folds transiently into alternative higher-order structures such as G-quadruplexes (G4s) and three-way DNA junctions (TWJs). G4s and TWJs can be stabilised by small molecules (ligands) that have high chemotherapeutic potential, either as standalone DNA damaging agents or combined in synthetic lethality strategies. While previous approaches have claimed to use ligands that specifically target either G4s or TWJs, we report here on a new approach in which ligands targeting both TWJs and G4s in vitro demonstrate cellular effects distinct from that of G4 ligands, and attributable to TWJ targeting. The DNA binding modes of these new, dual TWJ-/G4-ligands w…

Impairment of antioxidant enzymes, lipid peroxidation and 8-oxo-2'-deoxyguanosine in advanced epithelial ovarian carcinoma of a Spanish community.

2006

In the present study, we describe the changes of antioxidant enzyme activities and other oxidative stress-related parameters in a mediterranean cohort of women affected with epithelial ovarian carcinoma (EOC). For that purpose, the most representative enzymatic activities, such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and the oxidized/reduced glutathione (GSSG/GSH) ratio have been analyzed in tumor tissue biopsies and compared with the normal tissue of the same patient. As oxidation products, the levels of malondialdehyde (MDA) as an indication of lipid peroxidation, and the DNA damaged base 8-oxo-2'-deoxyguanosine (8-oxo-dG) have been also measured. Ad…

Induction of heme oxygenase-1 and adaptive protection against the induction of DNA damage after hyperbaric oxygen treatment.

2000

Hyperbaric oxygen (HBO) treatment of human subjects (i.e. exposure to 100% oxygen at a pressure of 2.5 ATA for a total period of 3 x 20 min) caused clear and reproducible DNA damage in lymphocytes, as detected with the comet assay (single cell gel electrophoresis). Induction of DNA damage was found only after the first HBO exposure and not after further treatments of the same individuals. Furthermore, blood taken 24 h after HBO treatment was significantly protected against the induction of DNA damage by hydrogen peroxide (H(2)O(2)) in vitro, indicating that adaptation occurred due to induction of antioxidant defenses. The cells were not significantly protected against the genotoxic effects …