Nuclear DNA damages generated by reactive oxygen molecules (ROS) under oxidative stress and their relevance to human cancers, including ionizing radiation-induced neoplasia part II: Relation between ROS-induced DNA damages and human cancer

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.

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Glucose deprivation increases nuclear DNA repair protein Ku and resistance to radiation induced oxidative stress in human cancer cells

Cell Biochemistry and Function ◽

10.1002/cbf.1541 ◽

2009 ◽

Vol 27 (2) ◽

pp. 93-101 ◽

Cited By ~ 18

Author(s):

Jie Li ◽

Roashan Ayene ◽

Kathleen M. Ward ◽

Eswarkumar Dayanandam ◽

Iraimoudi S. Ayene

Keyword(s):

Oxidative Stress ◽

Dna Repair ◽

Cancer Cells ◽

Nuclear Dna ◽

Human Cancer ◽

Glucose Deprivation ◽

Human Cancer Cells ◽

Repair Protein ◽

Dna Repair Protein ◽

Radiation Induced

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Involvement of reactive oxygen species in ionizing radiation–induced upregulation of cell surface Toll-like receptor 2 and 4 expression in human monocytic cells

Journal of Radiation Research ◽

10.1093/jrr/rrx011 ◽

2017 ◽

Vol 58 (5) ◽

pp. 626-635 ◽

Cited By ~ 8

Author(s):

Hironori Yoshino ◽

Ikuo Kashiwakura

Keyword(s):

Reactive Oxygen Species ◽

Protein Synthesis ◽

Ionizing Radiation ◽

Cell Surface ◽

Reactive Oxygen ◽

Mitogen Activated Protein Kinase ◽

Protein Synthesis Inhibitor ◽

Oxygen Species ◽

X Ray ◽

Radiation Induced

Abstract Toll-like receptors (TLRs) are pattern recognition receptors that recognize pathogen-associated molecular patterns and are indispensable for antibacterial and antiviral immunity. Our previous report showed that ionizing radiation increases the cell surface expressions of TLR2 and TLR4 and enhances their responses to agonists in human monocytic THP1 cells. The present study investigated how ionizing radiation increases the cell surface expressions of TLR2 and TLR4 in THP1 cells. The THP1 cells treated or not treated with pharmaceutical agents such as cycloheximide and N-acetyl-L-cysteine (NAC) were exposed to X-ray irradiation, following which the expressions of TLRs and mitogen-activated protein kinase were analyzed. X-ray irradiation increased the mRNA expressions of TLR2 and TLR4, and treatment with a protein synthesis inhibitor cycloheximide abolished the radiation-induced upregulation of their cell surface expressions. These results indicate that radiation increased those receptors through de novo protein synthesis. Furthermore, treatment with an antioxidant NAC suppressed not only the radiation-induced upregulation of cell surface expressions of TLR2 and TLR4, but also the radiation-induced activation of the c-Jun N-terminal kinase (JNK) pathway. Since it has been shown that the inhibitor for JNK can suppress the radiation-induced upregulation of TLR expression, the present results suggest that ionizing radiation increased the cell surface expressions of TLR2 and TLR4 through reactive oxygen species–mediated JNK activation.

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Ionizing Radiation-Induced Oxidative Stress Alters miRNA Expression

PLoS ONE ◽

10.1371/journal.pone.0006377 ◽

2009 ◽

Vol 4 (7) ◽

pp. e6377 ◽

Cited By ~ 237

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

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Nuclear Abl Drives miR-34c Transfer by Extracellular Vesicles to Induce Radiation Bystander Effects

10.1101/209767 ◽

2017 ◽

Author(s):

Shubhra Rastogi ◽

Amini Hwang ◽

Josolyn Chan ◽

Jean YJ Wang

Keyword(s):

Reactive Oxygen Species ◽

Dna Damage ◽

Ionizing Radiation ◽

Extracellular Vesicles ◽

Reactive Oxygen ◽

Nuclear Accumulation ◽

Oxygen Species ◽

Bystander Effects ◽

Abl Tyrosine Kinase ◽

Radiation Induced

SUMMARYIonizing radiation stimulates nuclear accumulation of Abl tyrosine kinase that is required for directly irradiated cells to produce microRNA-34c-containing extracellular vesicles, which transfer the microRNA into non-irradiated cells to induce reactive oxygen species and bystander DNA damage.ABSTRACTIonizing radiation (IR) activates an array of DNA damage response (DDR) that includes the induction of bystander effects (BE) in cells not targeted by radiation. How DDR pathways in irradiated cells stimulate BE in non-targeted cells is mostly unknown. We show here that extracellular vesicles from irradiated cells (EV-IR) induce reactive oxygen species (ROS) and DNA damage when internalized by un-irradiated cells. We found that EV-IR from Abl-NLS-mutated cells could not induce ROS or DNA damage, and restoration of nuclear Abl rescued those defects. Expanding a previous finding that Abl stimulates miR-34c expression, we show here that nuclear Abl also drives the vesicular secretion of miR-34c. Ectopic miR-34c expression, without irradiation, generated EV-miR-34c capable of inducing ROS and DNA damage. Furthermore, EV-IR from miR34-knockout cells could not induce ROS and raised γH2AX to lesser extent than EV-IR from miR34-wild type cells. These results establish a novel role for the Abl-miR-34c DDR pathway in stimulating radiation-induced bystander effects.

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Ascorbic Acid 2-Glucoside Pretreatment Protects Cells from Ionizing Radiation, UVC, and Short Wavelength of UVB

Genes ◽

10.3390/genes11030238 ◽

2020 ◽

Vol 11 (3) ◽

pp. 238 ◽

Cited By ~ 5

Author(s):

Junko Maeda ◽

Allison J. Allum ◽

Jacob T. Mussallem ◽

Coral E. Froning ◽

Alexis H. Haskins ◽

...

Keyword(s):

Ascorbic Acid ◽

Ionizing Radiation ◽

Uv Light ◽

Chinese Hamster ◽

Radical Scavenger ◽

Protective Effects ◽

Wild Type ◽

Dna Damages ◽

Narrowband Uvb ◽

Radiation Induced

Ascorbic acid 2-glucoside (AA2G), glucosylated ascorbic acid (AA), has superior properties for bioavailability and stability compared to AA. Although AA2G has shown radioprotective properties similar to AA, effects for UV light, especially UVC and UVB, are not studied. AA2G was tested for cytotoxicity and protective effects against ionizing radiation, UVC, and broadband and narrowband UVB in Chinese hamster ovary (CHO) cells and compared to AA and dimethyl sulfoxide (DMSO). Pretreatment with DMSO, AA, and AA2G showed comparative protective effects in CHO wild type and radiosensitive xrs5 cells for cell death against ionizing radiation with reducing the number of radiation-induced DNA damages. Pretreatment with AA and AA2G protected CHO wild type and UV sensitive UV135 cells from UVC and broadband UV, but not from narrowband UVB. DMSO showed no protective effects against tested UV. The UV filtration effects of AA and AA2G were analyzed with a spectrometer and spectroradiometer. AA and AA2G blocked UVC and reduced short wavelengths of UVB, but had no effect on wavelengths above 300 nm. These results suggest that AA2G protects cells from radiation by acting as a radical scavenger to reduce initial DNA damage, as well as protecting cells from certain UVB wavelengths by filtration.

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