Zeylenone synergizes with cisplatin in osteosarcoma by enhancing DNA damage, apoptosis, and necrosis via the Hsp90/ AKT / GSK3β and Fanconi anaemia pathway

2021 ◽  
Author(s):  
Shuxian Yang ◽  
Haiyan Xiao ◽  
Yunfang Sun ◽  
Li Cao
Keyword(s):  
Dna Damage ◽  
Fanconi Anaemia ◽  
Apoptosis And Necrosis

scholarly journals Deleterious effect of mercuric chloride on human epithelial cells

2021 ◽  
Author(s):  
Changhai (Kevin) Ji
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Epithelial Cells ◽  
Human Health ◽  
Exposure Time ◽  
Mercuric Chloride ◽  
Deleterious Effect ◽  
Detection Techniques ◽  
Human Epithelial Cells ◽  
Apoptosis And Necrosis

This thesis studied the cytotoxicity of mercuric chloride on human epihelial cells. The three detection techniques were developed to monitor the cytotoxicity of soluble mercuric chloride to human health. Both increased concentration and exposure time resulted in increased DNA damage and cell death. At lower levels death occurred by a mixture of apoptosis and necrosis, while at higher levels cell death occurred primarily by necrosis. This is the first study to demonstrate a deleterious effect of soluble mercuric chloride on human epithelial cells, although mercury has long been known as nephrotoxic and neurotoxic.

In vitro assessment of anticytotoxic and antigenotoxic effects of CANOVA®

Homeopathy ◽  
2016 ◽  
Vol 105 (03) ◽  
pp. 265-269 ◽  
Author(s):  
Henrique Fonseca Sousa do Nascimento ◽  
Plínio Cerqueira dos Santos Cardoso ◽  
Helem Ferreira Ribeiro ◽  
Tatiane Cristina Mota ◽  
Lorena Monteiro Gomes ◽  
...  
Keyword(s):  
Dna Damage ◽  
Human Lymphocytes ◽  
Nitroso Compound ◽  
Cytoprotective Effect ◽  
In Vitro Assessment ◽  
Induced Apoptosis ◽  
Clinical Conditions ◽  
Apoptosis And Necrosis ◽  
Antigenotoxic Effects

Background: CANOVA® (CA) is a homeopathic immunomodulator. It contains several homeopathic medicines prepares according to the Brazilian Pharmacopoeia. CA is indicated in clinical conditions in which the immune system is impaired and against tumors. N-methyl-N-nitrosourea (NMU) is an N-nitroso compound, with genotoxic/mutagenic properties. Although several studies have shown promising results in the use of CA, there are no studies reporting possible antigenotoxic effects. Method: This study evaluated the in vitro antigenotoxic and anticytotoxic effects of CA in human lymphocytes exposed to NMU. Samples of human lymphocytes that were subjected to different concentrations of a mixture containing CA and NMU were used. The genotoxicity/antigenotoxicity of CA was evaluated by the comet assay, anticytotoxicity was assessed by quantification of apoptosis and necrosis using acridine orange/ethidium bromide. Results: CA significantly reduced DNA damage induced by NMU and reduced significantly the frequency of NMU-induced apoptosis after 24 h of treatment. Conclusion: CA has an important cytoprotective effect significantly reducing the DNA damage and apoptosis induced by the carcinogen NMU.

Capillary electrophoresis of DNA damage after irradiation: apoptosis and necrosis

2000 ◽  
Vol 871 (1-2) ◽  
pp. 321-330 ◽  
Author(s):  
Marı́a Teresa Valenzuela ◽  
Marı́a Isabel Núñez ◽  
Marı́a Rosario Guerrero ◽  
Mercedes Villalobos ◽  
José Mariano Ruiz de Almodóvar
Keyword(s):  
Dna Damage ◽  
Capillary Electrophoresis ◽  
Apoptosis And Necrosis

DNA damage in lead-exposed hepatocytes: coexistence of apoptosis and necrosis?

2011 ◽  
Vol 35 (2) ◽  
pp. 208-217 ◽  
Author(s):  
Kilarkaje Narayana ◽  
Raj Raghupathy
Keyword(s):  
Dna Damage ◽  
Apoptosis And Necrosis

scholarly journals Evolution, structure and emerging roles of C1ORF112 in DNA replication, DNA damage responses, and cancer

2021 ◽  
Author(s):  
Jacob Edogbanya ◽  
Daniela Tejada‐Martinez ◽  
Nigel J. Jones ◽  
Amit Jaiswal ◽  
Sarah Bell ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Replication ◽  
Current Knowledge ◽  
Future Research ◽  
Fanconi Anaemia ◽  
Mammalian Development ◽  
Damage Repair ◽  
Disease Relevance ◽  
Helical Protein ◽  
Cycle Regulation

AbstractThe C1ORF112 gene initially drew attention when it was found to be strongly co‐expressed with several genes previously associated with cancer and implicated in DNA repair and cell cycle regulation, such as RAD51 and the BRCA genes. The molecular functions of C1ORF112 remain poorly understood, yet several studies have uncovered clues as to its potential functions. Here, we review the current knowledge on C1ORF112 biology, its evolutionary history, possible functions, and its potential relevance to cancer. C1ORF112 is conserved throughout eukaryotes, from plants to humans, and is very highly conserved in primates. Protein models suggest that C1ORF112 is an alpha-helical protein. Interestingly, homozygous knockout mice are not viable, suggesting an essential role for C1ORF112 in mammalian development. Gene expression data show that, among human tissues, C1ORF112 is highly expressed in the testes and overexpressed in various cancers when compared to healthy tissues. C1ORF112 has also been shown to have altered levels of expression in some tumours with mutant TP53. Recent screens associate C1ORF112 with DNA replication and reveal possible links to DNA damage repair pathways, including the Fanconi anaemia pathway and homologous recombination. These insights provide important avenues for future research in our efforts to understand the functions and potential disease relevance of C1ORF112.

scholarly journals DNA damage and cellular abnormalities in tuberculosis, lung cancer and chronic obstructive pulmonary disease

2015 ◽  
Vol 10 ◽  
Author(s):  
Andréa Lúcia Gonçalves da Silva ◽  
Maribel Josimara Bresciani ◽  
Thaís Evelyn Karnopp ◽  
Augusto Ferreira Weber ◽  
Joel Henrique Ellwanger ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Damage ◽  
Low Frequency ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Chronic Obstructive Pulmonary Diseases ◽  
Cellular Abnormalities ◽  
Apoptosis And Necrosis ◽  
Cytome Assay

Background: Tuberculosis (TB), Lung Cancer (LC) and Chronic Obstructive Pulmonary Diseases (COPD) affect millions of individuals worldwide. Monitoring of DNA damage in pathological situations has been investigated because it can add a new dimension to clinical expression and may represent a potential target for therapeutic intervention. The aim of this study was to evaluate DNA damage and the frequency of cellular abnormalities in TB, LC and COPD patients by comparing them to healthy subjects. Methods: The detection of DNA damage by a buccal micronucleus cytome assay was investigated in patients with COPD (n = 28), LC (n = 18) and TB (n = 22) and compared to control individuals (n = 17). Results: The COPD group had a higher frequency of apoptotic cells compared to TB and LC group. The TB group showed a higher frequency of DNA damage, defect in cytokinesis, apoptotic and necrotic cells. Patients with LC had low frequency of chromosomal aberrations than TB and COPD patients. Conclusion: COPD patients showed cellular abnormalities that corresponded to cell death by apoptosis and necrosis, while patients with TB presented defects in cytokinesis and dysfunctions in DNA repair that resulted in the formation of micronucleus (MN) besides apoptotic and necrotic cells. Patients with COPD, TB and LC had a low frequency of permanent DNA damage.

scholarly journals Depletion of ATP and Oxidative Stress Underlie Zinc-Induced Cell Injury

2007 ◽  
Vol 50 (1) ◽  
pp. 43-49 ◽  
Author(s):  
Emil Rudolf
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Cell Death ◽  
Nadph Oxidase ◽  
Cell Injury ◽  
Atp Depletion ◽  
Atp Production ◽  
Apoptosis And Necrosis ◽  
Positive Effect ◽  
And Oxidative Stress

The mechanisms of cell injury resulting in a special type of cell death combining the features of apoptosis and necrosis were examined in Hep-2 cells exposed to 300 μM zinc sulfate during 24h. Acute exposure to zinc induced a rapid rise in metallothionein levels and increased oxidative stress occurring in the absence of a significant early ATP depletion. Accentuated ATP loss and elevated levels of superoxide at later treatment intervals (12h and longer) were present along with increased DNA damage. Manipulation with ATP production and inhibition of NADPH oxidase had a positive effect on zinc-related increase in oxidative stress and influenced the observed type of cell death. These results suggest that Hep-2 cells acutely exposed to zinc increase intracellular labile zinc stores and over express metalothioneins. Elevated production of peroxides in zinc-treated cells is at later treatment intervals accompanied by an increase in superoxide levels, possibly by activation of NADPH oxidase, DNA damage and severe ATP loss. Prevention of critical ATP depletion and, in particular, inhibition of oxidative stress attenuates zinc-mediated cell injury and stimulates apoptosis-like phenotype in exposed cells.

The role of p53 and cell death by apoptosis and necrosis in 4-hydroperoxycyclophosphamide-induced limb malformations

Development ◽  
1998 ◽  
Vol 125 (16) ◽  
pp. 3225-3234
Author(s):  
S.A. Moallem ◽  
B.F. Hales
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Death ◽  
Drug Treatment ◽  
Cell Cycle Arrest ◽  
Wild Type ◽  
Cycle Arrest ◽  
Limb Malformations ◽  
Apoptosis And Necrosis

The exposure of embryonic murine limbs in vitro to an activated analog of cyclophosphamide, 4-hydroperoxycyclophosphamide (4OOH-CPA), induced limb malformations and apoptosis. The purpose of this study was to investigate the role of the tumor suppressor/cell cycle checkpoint gene, p53, and of cell cycle arrest in the response of the limbs to cyclophosphamide. Limbs, excised on day 12 of gestation from wild-type, heterozygous or homozygous p53-knockout transgenic murine embryos, were treated with vehicle (water) or 4OOH-CPA (0.3, 1.0 or 3.0 microgram/ml) and cultured for 6 days. Exposure of wild-type (+/+) limbs to 4OOH-CPA resulted in limb malformations, and reduced limb areas and developmental scores. The homozygous (−/−) limbs were dramatically more sensitive to the effects of 4OOH-CPA, as assessed by limb morphology, area and score. Heterozygous limbs exposed to the drug were intermediate for each parameter. Apoptosis, as assessed by the formation of a DNA ladder, was increased in drug-exposed wild-type limbs, but not in the drug-exposed homozygous limbs. Light and electron microscopy examination of the limbs revealed that drug treatment of wild-type limbs induced the morphological changes typical of apoptosis, particularly in the interdigital regions. In contrast, there was no evidence of apoptosis in homozygous limbs exposed to 4-OOH-CPA; morphological characteristics of necrosis such as cell membrane breakdown, mitochondrial swelling and cellular disintegration were evident throughout these limbs. Heterozygous limbs had cells dying with the characteristics of both apoptosis and necrosis. Fragments of poly(ADP-ribose) polymerase characteristic of necrosis predominated in the drug-treated heterozygous and homozygous limbs. 4-OOH-CPA-treatment of limbs from wild-type embryos led to arrest of the cell cycle at the G1/S phase. No cell cycle arrest was observed after drug treatment of homozygous limbs, in which populations of cells in S and G2/M phases, as well as a population of sub G1 cells, were found. Thus, the presence of p53 and of p53-dependent apoptosis protect organogenesis-stage limbs from insult with a teratogen. The absence of p53 may decrease DNA repair capacity and contribute to the accumulation of DNA damage in limb cells and their daughter cells; the failure of apoptosis to eliminate cells with DNA damage may result in increased cell death by necrosis and major limb malformations.

scholarly journals RDNA-12. THE FANCONI ANAEMIA (FA) PATHWAY AND GLIOBLASTOMA: A NEW FOUNDATION FOR DNA DAMAGE RESPONSE TARGETED COMBINATIONS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi209-vi209 ◽  
Author(s):  
Ola Rominiyi ◽  
Katie Myers ◽  
Natividad Gomez-Roman ◽  
Nikita Lad ◽  
Dawoud Dar ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Parp Inhibitor ◽  
Treatment Resistance ◽  
Predictive Biomarker ◽  
Fanconi Anaemia ◽  
Normal Brain ◽  
Strand Breaks ◽  
Pathway Gene ◽  
Damage Response

Abstract Treatment resistance in glioblastoma is underpinned by highly interconnected DNA damage response (DDR) processes. The FA-pathway is a fundamental DDR process required for the resolution of replication fork impeding lesions, and we have previously shown that it is inactive in normal brain, but is re-activated in glioblastoma, providing a cancer-specific target for combination DDR therapies. Here, we find that elevated FA-pathway gene expression in gliomas is associated with poor survival (-17.1% 5-year OS, p< 0.0001, n=329–REMBRANT). Furthermore, patient-derived glioblastoma stem cell (GSC) populations, which drive therapeutic resistance, display high FA-pathway expression relative to paired bulk tumour cell populations (mean 2.3-fold higher across genes, p=0.0073). We further show that inhibition of a single DDR process (FA-pathway, PARP, ATR or ATM) increases the susceptibility of glioblastoma cell lines and patient-derived GSCs to current adjuvant therapy. Importantly, clinically approved PARP inhibitor (PARPi) monotherapy stimulates robust FANCD2 mono-ubiquitination, supporting a role of FA-pathway activation in response to current DDR-targeted therapy. In clinically-relevant 3D GSC models, simultaneous inhibition of the FA-pathway (FAPi) and PARP or ATR enhanced temozolomide sensitisation compared to a single DDR inhibitor (DDRi). Furthermore, combined FAPi+PARPi consistently conferred radiosensitisation whilst combined FAPi+ATRi led to a profoundly radiosensitising effect; e.g. sensitizer enhancement ratio (SER0.37) of 3.23 (3.03–3.49, 95% CI). Furthermore, comparison of α/β ratio enhancement suggests dual-DDRi strategies fundamentally alter the response of GSCs, whilst single cell gel electrophoresis & immunofluorescence studies suggest FA-pathway based DDRi combinations profoundly delay the resolution of IR-induced DNA strand breaks at 6 hours post-treatment, with increased persistent DNA double strand breaks at 24 hours. In conclusion, simultaneously targeting the FA-pathway and interconnected DDR processes represents an appealing therapeutic strategy. Additionally, constitutive lack of FA pathway function in some tumours, could serve as a novel predictive biomarker for patient response to PARPi and ATRi currently in clinical trials.

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