scholarly journals Hydrogen peroxide mediates the radiation-induced mutator phenotype in mammalian cells

2008 ◽  
Vol 413 (1) ◽  
pp. 185-191 ◽  
Author(s):  
Disha Dayal ◽  
Sean M. Martin ◽  
Charles L. Limoli ◽  
Douglas R. Spitz
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Ionizing Radiation ◽  
Mammalian Cells ◽  
Mutation Frequency ◽  
Fold Increase ◽  
Mutator Phenotype ◽  
Chronic Oxidative Stress ◽  
Dose Dependent Fashion ◽  
Radiation Induced

Chronic oxidative stress has been associated with genomic instability following exposure to ionizing radiation. However, results showing direct causal linkages between specific ROS (reactive oxygen species) and the ionizing radiation-induced mutator phenotype are lacking. The present study demonstrates that ionizing radiation-induced genomically unstable cells (characterized by chromosomal instability and an increase in mutation and gene amplification frequencies) show a 3-fold increase in steady-state levels of hydrogen peroxide, but not superoxide. Furthermore, stable clones isolated from parallel studies showed significant increases in catalase and GPx (glutathione peroxidase) activity. Treatment of unstable cells with PEG-CAT (polyethylene glycol-conjugated catalase) reduced the mutation frequency and mutation rate in a dose-dependent fashion. In addition, inhibiting catalase activity in the stable clones using AT (3-aminotriazole) increased mutation frequency and rate. These results clearly demonstrate the causal relationship between chronic oxidative stress mediated by hydrogen peroxide and the mutator phenotype that persists for many generations following exposure of mammalian cells to ionizing radiation.

scholarly journals Molecular cloning of the cDNA for a mutant mouse ribonucleotide reductase M1 that produces a dominant mutator phenotype in mammalian cells.

1988 ◽  
Vol 8 (7) ◽  
pp. 2698-2704 ◽  
Author(s):  
I W Caras ◽  
D W Martin
Keyword(s):  
Ribonucleotide Reductase ◽  
Mammalian Cells ◽  
Mutant Mouse ◽  
Chinese Hamster Ovary Cells ◽  
Spontaneous Mutation ◽  
Single Point ◽  
Chinese Hamster ◽  
Fold Increase ◽  
Single Point Mutation ◽  
Mutator Phenotype

Mammalian ribonucleotide reductase is regulated by the binding of dATP and other nucleotide effectors to allosteric sites on subunit M1. Using mRNA from a mutant mouse T-lymphoma (S49) cell line, we have isolated a cDNA which encodes an altered, dATP feedback-resistant subunit M1. The mutant cDNA contains a single point mutation (a G-to-A transition) at codon 57, converting aspartic acid to asparagine. Proof that this mutation is responsible for the phenotype of dATP feedback resistance is provided by the following evidence. (i) The mutation was detected only in mutant S49 cells containing dATP feedback-resistant ribonucleotide reductase and not in wild-type or other mutant S49 cells. (ii) Transfection of Chinese hamster ovary cells with an expression plasmid containing the mutant M1 cDNA resulted in the production of dATP feedback-resistant ribonucleotide reductase. Transfected CHO cells expressing the mutant M1 cDNA exhibited a 15- to 25-fold increase in the frequency of spontaneous mutation to 6-thioguanine resistance, confirming that dATP feedback-resistant ribonucleotide reductase produces a mutator phenotype in mammalian cells. The availability of a cDNA which encodes dATP feedback-resistant subunit M1 thus provides a means of manipulating by transfection the frequency of spontaneous mutation in mammalian cells.

Flavonoids, the Family of Plant-derived Antioxidants making inroads into Novel Therapeutic Design against IR-induced Oxidative Stress in Parkinson’s Disease

2021 ◽  
Vol 19 ◽  
Author(s):  
Tapan Behl ◽  
Gagandeep Kaur ◽  
Aayush Sehgal ◽  
Gokhan Zengin ◽  
Sukhbir Singh ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Ionizing Radiation ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Radiation Induced ◽  
Novel Therapeutic

Background: Ionizing radiation from telluric sources is unceasingly an unprotected pitfall to humans. Thus, the foremost contributors to human exposure are global and medical radiations. Various pieces of evidences assembled during preceding years reveal the pertinent role of ionizing radiation-induced oxidative stress in the progression of neurodegenerative insults such as Parkinson’s disease, which have been contributing to increased proliferation and generation of reactive oxygen species. Objective: This review delineates the role of ionizing radiation-induced oxidative stress in Parkinson’s disease and proposes novel therapeutic interventions of flavonoid family offering effective management and slowing down the progression of Parkinson’s disease. Method: Published papers were searched via MEDLINE, PubMed, etc. published to date for in-depth database collection. Results: The potential of oxidative damage may harm the non-targeted cells. It can also modulate the functions of central nervous system, such as protein misfolding, mitochondria dysfunction, increased levels of oxidized lipids, and dopaminergic cell death, which accelerates the progression of Parkinson’s disease at the molecular, cellular, or tissue levels. In Parkinson’s disease, reactive oxygen species exacerbate the production of nitric oxides and superoxides by activated microglia, rendering death of dopaminergic neuronal cell through different mechanisms. Conclusion: Rising interest has extensively engrossed on the clinical trial designs based on the plant derived family of antioxidants. They are known to exert multifarious impact either way in neuroprotection via directly suppressing ionizing radiation-induced oxidative stress and reactive oxygen species production or indirectly increasing the dopamine levels and activating the glial cells.

scholarly journals Ionizing Radiation-Induced Oxidative Stress Alters miRNA Expression

PLoS ONE ◽  
2009 ◽  
Vol 4 (7) ◽  
pp. e6377 ◽  
Author(s):  
Nicole L. Simone ◽  
Benjamin P. Soule ◽  
David Ly ◽  
Anthony D. Saleh ◽  
Jason E. Savage ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ionizing Radiation ◽  
Mirna Expression ◽  
Radiation Induced

scholarly journals Molecular Markers of Ionizing Radiation-Induced Gene Mutations in Mammalian Cells

1996 ◽  
Vol 104 ◽  
pp. 675 ◽  
Author(s):  
Abraham W. Hsie ◽  
Ronald C. Porter ◽  
Zhidong Xu ◽  
Yonjia Yu ◽  
Juan Sun ◽  
...  
Keyword(s):  
Molecular Markers ◽  
Ionizing Radiation ◽  
Mammalian Cells ◽  
Gene Mutations ◽  
Radiation Induced

Radiation-induced kidney injury: a role for chronic oxidative stress?

Micron ◽  
2002 ◽  
Vol 33 (2) ◽  
pp. 133-141 ◽  
Author(s):  
Mike E.C Robbins ◽  
Weiling Zhao ◽  
Charles S Davis ◽  
Shinya Toyokuni ◽  
Stephen M Bonsib
Keyword(s):  
Oxidative Stress ◽  
Kidney Injury ◽  
Chronic Oxidative Stress ◽  
Radiation Induced

Effects of antioxidant nutrients on ionizing radiation-induced oxidative stress

Toxicology ◽  
2021 ◽  
pp. 307-316
Author(s):  
Tiziana Cervelli ◽  
Giuseppina Basta ◽  
Serena Del Turco
Keyword(s):  
Oxidative Stress ◽  
Ionizing Radiation ◽  
Radiation Induced

Febuxostat, an inhibitor of xanthine oxidase, ameliorates ionizing radiation-induced lung injury by suppressing caspase-3, oxidative stress and NF-κB

2021 ◽  
pp. 1-8
Author(s):  
Marziyeh Raeispour ◽  
Fereshteh Talebpour Amiri ◽  
Soghra Farzipour ◽  
Arash Ghasemi ◽  
Seyed Jalal Hosseinimehr
Keyword(s):  
Oxidative Stress ◽  
Ionizing Radiation ◽  
Lung Injury ◽  
Xanthine Oxidase ◽  
Caspase 3 ◽  
Radiation Induced
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