Search results for "cycle"
showing 10 items of 3119 documents
Compromised repair of radiation-induced DNA double-strand breaks in Fanconi anemia fibroblasts in G2
2020
Fanconi anemia (FA) is a rare chromosomal instability syndrome with various clinical features and high cancer incidence. Despite being a DNA repair disorder syndrome and a frequently observed clinical hypersensitivity of FA patients towards ionizing radiation, the experimental evidence regarding the efficiency of radiation-induced DNA double-strand break (DSB) repair in FA is very controversial. Here, we performed a thorough analysis of the repair of radiation-induced DSBs in G1 and G2 in FA fibroblasts of complementation groups A, C, D1 (BRCA2), D2, E, F, G and P (SLX4) in comparison to normal human lung and skin fibroblasts. γH2AX, 53BP1, or RPA foci quantification after X-irradiation was…
Role of glutathione in cell nucleus
2010
Cells with high proliferation rate have high glutathione levels. This typical feature of cancer cells is viewed usually as a defence mechanism against ionizing radiation or chemotherapy. Efforts have been made in order to decrease cellular glutathione levels in tumours as a necessary pre-treatment for cancer therapy. However, very few reports have considered cellular glutathione as a physiological tool for cells to proliferate and that most of this high glutathione levels were located in the nucleus. The role of nuclear glutathione in cell physiology has become more important in the last years. This review summarizes new findings that point to the nuclear reduced status as an environment th…
Circadian rhythms and chemical carcinogenesis: Potential link. An overview.
2009
Circadian rhythm is an integral and not replaceable part of the organism's homeostasis. Its signalling is multidimensional, overlooking global networks such as chromatin remodelling, cell cycle, DNA damage and repair as well as nuclear receptors function. Understanding its global networking will allow us to follow up not only organism dysfunction and pathology (including chemical carcinogenesis) but well-being in general having in mind that time is not always on our side. The authors thank ECNIS (Environmental Cancer, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5: Food Quality and Safety (Contract no. …
Cell proliferation and DNA breaks are involved in ultraviolet light-induced apoptosis in nucleotide excision repair-deficient Chinese hamster cells.
2002
UV light targets both membrane receptors and nuclear DNA, thus evoking signals triggering apoptosis. Although receptor-mediated apoptosis has been extensively investigated, the role of DNA damage in apoptosis is less clear. To analyze the importance of DNA damage induced by UV-C light in apoptosis, we compared nucleotide excision repair (NER)-deficient Chinese hamster ovary cells (lines 27-1 and 43-3B mutated for the repair genes ERCC3 and ERCC1, respectively) with the corresponding DNA repair-proficient fibroblasts (CHO-9 and ERCC1 complemented 43-3B cells). NER-deficient cells were hypersensitive as to the induction of apoptosis, indicating that apoptosis induced by UV-C light is due to u…
Mechanisms and consequences of methylating agent-induced SCEs and chromosomal aberrations: a long road traveled and still a far way to go.
2003
Since the milestone work of Evans and Scott, demonstrating the replication dependence of alkylation-induced aberrations, and Obe and Natarajan, pointing to the critical role of DNA double-strand breaks (DSBs) as the ultimate trigger of aberrations, the field has grown extensively. A notable example is the identification of DNA methylation lesions provoking chromosome breakage (clastogenic) effects, which made it possible to model clastogenic pathways evoked by genotoxins. Experiments with repair-deficient mutants and transgenic cell lines revealed both O<sup>6</sup>-methylguanine (O<sup>6</sup>MeG) and N- methylpurines as critical lesions. For S<sub>N</sub&g…
Functional Inactivation of pRB Results in Aneuploid Mammalian Cells After Release From a Mitotic Block
2002
AbstractThe widespread chromosome instability observed in tumors and in early stage carcinomas suggests that aneuploidy could be a prerequisite for cellular transformation and tumor initiation. Defects in tumor suppressers and genes that are part of mitotic checkpoints are likely candidates for the aneuploid phenotype. By using flow cytometric, cytogenetic, immunocytochemistry techniques we investigated whether pRB deficiency could drive perpetual aneuploidy in normal human and mouse fibroblasts after mitotic checkpoint challenge by microtubule-destabilizing drugs. Both mouse and human pRB-deficient primary fibroblasts resulted, upon release from a mitotic block, in proliferating aneuploid …
Lovastatin protects human endothelial cells from the genotoxic and cytotoxic effects of the anticancer drugs doxorubicin and etoposide
2006
Background and purpose: 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are frequently used lipid-lowering drugs. Moreover, they exert pleiotropic effects on cellular stress responses and death. Here, we analysed whether lovastatin affects the sensitivity of primary human endothelial cells (HUVEC) to the anticancer drug doxorubicin. Experimental approach: We investigated whether pretreatment of HUVEC with low dose of lovastatin influences the cellular sensitivity to doxorubicin. To this end, cell viability, proliferation and apoptosis as well as DNA damage-triggered stress response were analysed. Key results: Lovastatin reduced the cytotoxic potency of doxorub…
A breakdown in macromolecular synthesis preceding differentiation in Streptomyces coelicolor A3(2)
1990
Summary: A transitory cessation of growth was recorded in Streptomyces coelicolor A3(2) at the end of vegetative mycelium formation on solid medium. In the same phase a striking reduction in protein and nucleic acid synthesis was detected. Growth and macromolecular synthesis resumed, nearly reaching the original values, when morphological differentiation occurred. It is concluded that a physiological stress occurs within the bacterial population just before the onset of the morphological differentiation.
The bacterial cytolethal distending toxin (CDT) triggers a G2 cell cycle checkpoint in mammalian cells without preliminary induction of DNA strand br…
1999
The bacterial cytolethal distending toxin (CDT) was previously shown to arrest the tumor-derived HeLa cell line in the G2-phase of the cell cycle through inactivation of CDK1, a cyclin-dependent kinase whose state of activation determines entry into mitosis. We have analysed the effects induced in HeLa cells by CDT, in comparison to those induced by etoposide, a prototype anti-tumoral agent that triggers a G2 cell cycle checkpoint by inducing DNA damage. Both CDT and etoposide inhibit cell proliferation and induces the formation of enlarged mononucleated cells blocked in G2. In both cases, CDK1 from arrested cells could be re-activated both in vitro by dephosphorylation by recombinant Cdc25…
The APC/C cofactor Cdh1 prevents replicative stress and p53-dependent cell death in neural progenitors
2013
The E3-ubiquitin ligase APC/C-Cdh1 is essential for endoreduplication but its relevance in the mammalian mitotic cell cycle is still unclear. Here we show that genetic ablation of Cdh1 in the developing nervous system results in hypoplastic brain and hydrocephalus. These defects correlate with enhanced levels of Cdh1 substrates and increased entry into the S phase in neural progenitors. However, cell division is prevented in the absence of Cdh1 due to hyperactivation of cyclin-dependent kinases, replicative stress, induction of p53, G2 arrest and apoptotic death of these progenitor cells. Concomitant ablation of p53 rescues apoptosis but not replicative stress, resulting in the presence of …