Search results for " DAMAGE"
showing 10 items of 1139 documents
Rapid inactivation and proteasome-mediated degradation of OGG1 contribute to the synergistic effect of hyperthermia on genotoxic treatments
2013
Inhibition of DNA repair has been proposed as a mechanism underlying heat-induced sensitization of tumour cells to some anticancer treatments. Base excision repair (BER) constitutes the main pathway for the repair of DNA lesions induced by oxidizing or alkylating agents. Here, we report that mild hyperthermia, without toxic consequences per se, affects cellular DNA glycosylase activities, thus impairing BER. Exposure of cells to mild hyperthermia leads to a rapid and selective inactivation of OGG1 (8-oxoguanine DNA glycosylase) associated with the relocalisation of the protein into a detergent-resistant cellular fraction. Following its inactivation, OGG1 is ubiquitinated and directed to pro…
Detection of DNA effects in human cells with the comet assay and their relevance for mutagenesis
1996
The single cell gel test (SCG-test or comet assay) is a rapid and sensitive method for measuring DNA damage and repair in individual cells. A wide variety of mutagens have been shown to cause DNA alterations detectable with the comet assay, but it is not yet clear whether a relationship exists between the DNA effects and the induction of mutations. We are therefore investigating in a cell culture system with human cells (MRC5CV1) the induction of DNA damage by environmental mutagens and the formation of mutations at the HPRT gene. In the present study we investigated benzo[a]pyrene (BP), an environmental mutagenic and carcinogenic polycyclic aromatic hydrocarbon, and its reactive metabolite…
Lessons from the 2018-2019 European droughts : a collective need for unifying drought risk management
2022
Funding Information: This open-access publication was funded by the University of Freiburg. Funding Information: Financial support. The project is supported by the Wassernetzwerk Baden-Württemberg (Water Research Network of the State Baden-Württemberg), which is funded by the Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg (Ministry of Science, Research and the Arts of the State Baden-Württemberg) (grant no. AZ. 7532.21/2.1.6) and Maa-ja vesitekniikan tuki ry foundation. Doris E. Wendt acknowledges her support as part of the NERC-funded Groundwater Drought Initiative (NE/R004994/1). Lucy J. Barker was supported by the Natural Environment Research Council (NE/R016429/1) a…
Increased oxidative stress is responsible for ether-lipid loss in the retina of senescence accelerated mouse (SAM)
2006
International audience; Purpose: Ether–lipids represent an important class of retinal phospholipids but their exact functions are still unknown. They might act as antioxidants since the vinyl–ether double bond they contain could be the target for newly formed oxygenated radicals. In this work, we investigated the status of ether–lipids and aldehydes, their oxidative degradation products in the retina of a mouse model for aging, the senescence–accelerated mouse prone 8 (SAM P8), in which we reported a reduction of retinal function following 12 months of age (ARVO 2004 E–abstract 797). We completed this study by evaluating the oxidative stress in the retina. Methods: The quantification of eth…
Styrene Metabolism, Genotoxicity, and Potential Carcinogenicity
2006
This report reviews styrene biotransformation, including minor metabolic routes, and relates metabolism to the genotoxic effects and possible styrene-related carcinogenicity. Styrene is shown to require metabolic activation in order to become notably genotoxic and styrene 7,8-oxide is shown to contribute quantitatively by far the most (in humans more than 95%) to the genotoxicity of styrene, while minor ring oxidation products are also shown to contribute to local toxicities, especially in the respiratory system. Individual susceptibility depending on metabolism polymorphisms and individual DNA repair capacity as well as the dependence of the nonlinearity of the dose-response relationships …
THIOPYRANO[2,3-E]INDOL-2-ONES: ANGELICIN HETEROANALOGUES WITH POTENT PHOTOANTIPROLIFERATIVE ACTIVITY
2008
A new class of compounds, the thiopyrano[2,3-e]indol-2-ones, bioisosters of the angular furocoumarin angelicin, was synthesized with the aim of obtaining new photochemotherapeutic agents. In particular 7,8-dimethyl-thiopyranoindolone 6c s showed a remarkable phototoxicity and a great dose UVA dependence reaching IC(50) values at submicromolar level. This latter photoinduced a massive apoptosis and a remarkable photodamage to lipids and proteins. Although it did not intercalate DNA, it was able to cause photooxidation of DNA bases.
Host–pathogen interactions in Vibrio vulnificus: responses of monocytes and vascular endothelial cells to live bacteria
2015
ABSTRACT Aim: To demonstrate that Vibrio vulnificus, a sepsis-related aquatic pathogen, can provoke a strong pro-inflammatory reaction in blood-associated target cells. Materials & methods: We selected two strains of the two main phylogenetic lineages, two human cell lines, monocytes and vascular endothelial cells and designed an in vitro infection model simulating early septicemia. Results: Both strains caused a strong cell-specific pro-inflammatory response and produced a high degree of cell damage that ended with death by lysis (endothelial cells) or apoptosis/lysis (monocytes). The interaction with endothelial cells was stronger than expected and significantly different for both l…
Pathophysiology of traumatic brain injury.
2007
The knowledge of the pathophysiology after traumatic head injury is necessary for adequate and patient-oriented treatment. As the primary insult, which represents the direct mechanical damage, cannot be therapeutically influenced, target of the treatment is the limitation of the secondary damage (delayed non-mechanical damage). It is influenced by changes in cerebral blood flow (hypo- and hyperperfusion), impairment of cerebrovascular autoregulation, cerebral metabolic dysfunction and inadequate cerebral oxygenation. Furthermore, excitotoxic cell damage and inflammation may lead to apoptotic and necrotic cell death. Understanding the multidimensional cascade of secondary brain injury offers…
An Interface Mechanical Model with a Cohesive to Frictional Transition
2009
A thermodynamically consistent mechanical interface model is presented. The model is based on the interface damage mechanic theory applied in a special fashion such that the interface damage variable is also used as a parameter which drives the continuous and smooth transition from the sound initial cohesive state to the final fully fractured frictional state. Interface damage activation and fictional sliding are promoted by a damage activation function and a Coulomb frictional yielding function. The main features of the model are discussed in details and some numerical results for the material response are shown in monotonic and cyclic loading regimes.
Study of the cytolethal distending toxin (CDT)-activated cell cycle checkpoint. Involvement of the CHK2 kinase.
2001
AbstractThe bacterial cytolethal distending toxin (CDT) triggers a G2/M cell cycle arrest in eukaryotic cells by inhibiting the CDC25C phosphatase-dependent CDK1 dephosphorylation and activation. We report that upon CDT treatment CDC25C is fully sequestered in the cytoplasmic compartment, an effect that is reminiscent of DNA damage-dependent checkpoint activation. We show that the checkpoint kinase CHK2, an upstream regulator of CDC25C, is phosphorylated and activated after CDT treatment. In contrast to what is observed with other DNA damaging agents, we demonstrate that the activation of CHK2 can only take place during S-phase. Use of wortmannin and caffeine suggests that this effect is no…