Search results for "DNA damage"

Human FOXP3 and cancer.

2010

FOXP3 is a transcription factor necessary and sufficient for induction of the immunosuppressive functions in regulatory T lymphocytes. Its expression was first considered as specific of this cell type, but FOXP3 can also be transiently expressed in T-cell antigen receptor-activated human nonregulatory T cells. Recent data indicate that FOXP3 is also expressed by some nonlymphoid cells, in which it can repress various oncogenes that are restored following FOXP3 deletion or mutation. This review summarizes major advances in (1) the understanding of Foxp3 functions in human regulatory T cells, (2) the prognostic significance of Foxp3-expressing T cells in human malignancies and (3) the signifi…

Abstract B63: Targeting cancer cells with a glucose-conjugated DNA repair inhibitor.

2011

Abstract Alkylating agents are important chemotherapeutic drugs used for the treatment of several types of cancers, including brain tumors, melanoma and lymphoma. These chemotherapeutic agents have a strong affinity towards oxygen atoms in DNA giving rise to the important genotoxic DNA lesions O6-methylguanine and O6-chloroethylguanine, which are responsible for the cytotoxic effects of several alkylating anticancer drugs (e.g. temozolomide and lomustine). The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) is considered as an important player of drug resistance because it removes these DNA adducts from the DNA. The MGMT protein restores guanine in the DNA by a suicide repa…

Ganciclovir-induced apoptosis in HSV-1 thymidine kinase expressing cells: critical role of DNA breaks, Bcl-2 decline and caspase-9 activation.

2002

Although ganciclovir (GCV) is most often used in suicide anticancer gene therapy, the mechanism of GCV-induced cell killing and apoptosis is not fully understood. We analysed the mechanism of apoptosis triggered by GCV using a model system of CHO cells stably transfected with HSV-1 thymidine kinase (HSVtk). GCV-induced apoptosis is due to incorporation of the drug into DNA resulting in replication-dependent formation of DNA double-strand breaks and, at later stages, S and G2/M arrest. GCV-provoked DNA instability was likely to be responsible for the observed initial decline in Bcl-2 level and caspase-9/-3 activation. Further decline in the Bcl-2 level was due to cleavage of the protein by c…

Human serum and erythrocytes protect white blood cells against DNA damage by ethylene oxide

1995

Intermittent and Periodic Fasting, Hormones, and Cancer Prevention

2021

Simple Summary Hormonal and growth factor alterations, related to an elevated food consumption and excessive adiposity, affect the regulation of genes involved in cellular processes including proliferation, differentiation and DNA repair, allowing cells to survive and proliferate despite the accumulation of mutations which lead to malignant transformation. The growth hormone/insulin growth factor-1 (GH/IGF-1)/ insulin pathway and its downstream effectors, in fact, are known to promote aging and/or age-related diseases, including cancer, in many model organisms. The restriction of nutrients is established to have strong effects on levels of hormones and growth factors, delaying the incidence…

Rad51 and BRCA2 - New Molecular Targets for Sensitizing Glioma Cells to Alkylating Anticancer Drugs

2011

First line chemotherapeutics for brain tumors (malignant gliomas) are alkylating agents such as temozolomide and nimustine. Despite growing knowledge of how these agents work, patients suffering from this malignancy still face a dismal prognosis. Alkylating agents target DNA, forming the killing lesion O(6)-alkylguanine, which is converted into DNA double-strand breaks (DSBs) that trigger apoptosis. Here we assessed whether inhibiting repair of DSBs by homologous recombination (HR) or non-homologous end joining (NHEJ) is a reasonable strategy for sensitizing glioma cells to alkylating agents. For down-regulation of HR in glioma cells, we used an interference RNA (iRNA) approach targeting Ra…

FISH and CHIPs: Colorful Clues to Radiation-Induced Chromosomal Instability

2004

Radiation produces a variety of clonal and non-clonal chromosome aberrations that can be characterized by fluorescence in situ hybridization (FISH). Epigenetic changes affecting the expression of an essential DNA repair gene(s) may be an importantant mechanism for radiation-induced chromosomal instability. Expression profiling with specialized cDNA chips promises to identify candidate genes for the delayed effects of radiation and to provide new insights into the manifold and complex cellular responses to DNA damage. Much progress can be made by using FISH and CHIPs to study the mechanisms and biological consequences of ionizing radiation.

Development and application of test methods for the detection of dietary constituents which protect against heterocyclic aromatic amines

2003

This article describes the development and use of assay models in vitro (genotoxicity assay with genetically engineered cells and human hepatoma (HepG2) cells) and in vivo (genotoxicity and short-term carcinogenicity assays with rodents) for the identification of dietary constituents which protect against the genotoxic and carcinogenic effects of heterocyclic aromatic amines (HAs). The use of genetically engineered cells expressing enzymes responsible for the bioactivation of HAs enables the detection of dietary factors that inhibit the metabolic activation of HAs. Human derived hepatoma (HepG2) cells are sensitive towards HAs and express several enzymes [glutathione S-transferase (GST), N-…

Potential role of oxidative DNA damage in the impact of PNPLA3 variant (rs 738409 CG) in hepatocellular carcinoma risk.

2014

International audience

Modulating effects of humic acids on genotoxicity induced by water disinfectants in Cyprinus carpio

2005

The use of chlorinated disinfectants during drinking-water production has been shown to generate halogenated compounds as a result of interactions of humic acids with chlorine. Such chlorinated by-products have been shown to induce genotoxic effects and consumption of chlorinated drinking-water has been correlated with increased risk for cancer induction in human populations. The aim of this work was to test the potential genotoxic effects on circulating erythrocytes of the fish Cyprinus carpio exposed in vivo to well-waters disinfected with sodium hypochlorite (NaClO), chlorine dioxide (ClO2) or peracetic acid (CH3COO2H, PAA), in the absence or presence of standard humic acids (HA). The ef…