scholarly journals Protective Effects of p53 Regulatory Agents Against High-LET Radiation-Induced Injury in Mice

2020 ◽  
Vol 8 ◽  
Author(s):  
Akinori Morita ◽  
Bing Wang ◽  
Kaoru Tanaka ◽  
Takanori Katsube ◽  
Masahiro Murakami ◽  
...  
Keyword(s):  
Cell Death ◽  
Radiation Injury ◽  
Ion Irradiation ◽  
Heavy Ion ◽  
Protective Effects ◽  
Iron Ion ◽  
Normal Tissues ◽  
High Let Radiation ◽  
High Let ◽  
Radiation Induced

Radiation damage to normal tissues is one of the most serious concerns in radiation therapy, and the tolerance dose of the normal tissues limits the therapeutic dose to the patients. p53 is well known as a transcription factor closely associated with radiation-induced cell death. We recently demonstrated the protective effects of several p53 regulatory agents against low-LET X- or γ-ray-induced damage. Although it was reported that high-LET heavy ion radiation (>85 keV/μm) could cause p53-independent cell death in some cancer cell lines, whether there is any radioprotective effect of the p53 regulatory agents against the high-LET radiation injury in vivo is still unclear. In the present study, we verified the efficacy of these agents on bone marrow and intestinal damages induced by high-LET heavy-ion irradiation in mice. We used a carbon-beam (14 keV/μm) that was shown to induce a p53-dependent effect and an iron-beam (189 keV/μm) that was shown to induce a p53-independent effect in a previous study. Vanadate significantly improved 60-day survival rate in mice treated with total-body carbon-ion (p < 0.0001) or iron-ion (p < 0.05) irradiation, indicating its effective protection of the hematopoietic system from radiation injury after high-LET irradiation over 85 keV/μm. 5CHQ also significantly increased the survival rate after abdominal carbon-ion (p < 0.02), but not iron-ion irradiation, suggesting the moderate relief of the intestinal damage. These results demonstrated the effectiveness of p53 regulators on acute radiation syndrome induced by high-LET radiation.

scholarly journals NADPH Oxidase Activation Contributes to Heavy Ion Irradiation–Induced Cell Death

Dose-Response ◽  
2017 ◽  
Vol 15 (1) ◽  
pp. 155932581769969 ◽  
Author(s):  
Yupei Wang ◽  
Qing Liu ◽  
Weiping Zhao ◽  
Xin Zhou ◽  
Guoying Miao ◽  
...  
Keyword(s):  
Cell Death ◽  
Nadph Oxidase ◽  
Ion Irradiation ◽  
Heavy Ion ◽  
Ros Generation ◽  
Heavy Ion Irradiation ◽  
Radiation Induced ◽  
Heavy Ion Radiation ◽  
Nox Family ◽  
Nadph Oxidase Activation

Increased oxidative stress plays an important role in heavy ion radiation–induced cell death. The mechanism involved in the generation of elevated reactive oxygen species (ROS) is not fully illustrated. Here we show that NADPH oxidase activation is closely related to heavy ion radiation–induced cell death via excessive ROS generation. Cell death and cellular ROS can be greatly reduced in irradiated cancer cells with the preincubation of diphenyleneiodium, an inhibitor of NADPH oxidase. Most of the NADPH oxidase (NOX) family proteins (NOX1, NOX2, NOX3, NOX4, and NOX5) showed increased expression after heavy ion irradiation. Meanwhile, the cytoplasmic subunit p47phox was translocated to the cell membrane and localized with NOX2 to form reactive NADPH oxidase. Our data suggest for the first time that ROS generation, as mediated by NADPH oxidase activation, could be an important contributor to heavy ion irradiation–induced cell death.

scholarly journals Furazolidone Increases Survival of Mice Exposed to Lethal Total Body Irradiation through the Antiapoptosis and Antiautophagy Mechanism

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Shumei Ma ◽  
Zhao Jin ◽  
Yi Liu ◽  
Lin Liu ◽  
Hao Feng ◽  
...  
Keyword(s):  
Cell Death ◽  
Total Body Irradiation ◽  
Radiation Injury ◽  
Lethal Dose ◽  
Epithelial Cell Line ◽  
Protective Effects ◽  
Intestinal Tissue ◽  
Radiation Induced ◽  
Total Body

Exposure to total body irradiation (TBI) causes dose- and tissue-specific lethality. However, there are few effective and nontoxic radiation countermeasures for the radiation injury. In the current study, mice were pretreated with a traditional antimicrobial agent, FZD, before TBI; the protective effects of FZD on radiation injury were evaluated by using parameters such as the spleen index and thymus index, immunohistochemical staining of intestinal tissue, and frequency of micronuclei in polychromatophilic erythrocytes of bone marrow. The intestinal epithelial cell line IEC-6 was used to investigate the underlying mechanisms. Our results indicated that FZD administration significantly improved the survival of lethal dose-irradiated mice, decreased the number of micronuclei, upregulated the number of leukocytes and immune organ indices, and restored intestinal integrity in mice after TBI. TUNEL and western blot showed that FZD protected intestinal tissue by downregulating radiation-induced apoptosis and autophagy. Meanwhile, FZD protected IEC-6 cells from radiation-induced cell death by inhibiting apoptosis and autophagy. To sum up, FZD protected against radiation-induced cell death both in vitro and in vivo through antiapoptosis and antiautophagy mechanisms.

scholarly journals Immunomodulatory Effects of Radiotherapy

2020 ◽  
Vol 21 (21) ◽  
pp. 8151
Author(s):  
Sharda Kumari ◽  
Shibani Mukherjee ◽  
Debapriya Sinha ◽  
Salim Abdisalaam ◽  
Sunil Krishnan ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Carbon Particle ◽  
Dna Lesions ◽  
X Rays ◽  
Adaptive Immune ◽  
High Let Radiation ◽  
Different Types ◽  
High Let ◽  
Radiation Induced ◽  
Tumor Death

Radiation therapy (RT), an integral component of curative treatment for many malignancies, can be administered via an increasing array of techniques. In this review, we summarize the properties and application of different types of RT, specifically, conventional therapy with x-rays, stereotactic body RT, and proton and carbon particle therapies. We highlight how low-linear energy transfer (LET) radiation induces simple DNA lesions that are efficiently repaired by cells, whereas high-LET radiation causes complex DNA lesions that are difficult to repair and that ultimately enhance cancer cell killing. Additionally, we discuss the immunogenicity of radiation-induced tumor death, elucidate the molecular mechanisms by which radiation mounts innate and adaptive immune responses and explore strategies by which we can increase the efficacy of these mechanisms. Understanding the mechanisms by which RT modulates immune signaling and the key players involved in modulating the RT-mediated immune response will help to improve therapeutic efficacy and to identify novel immunomodulatory drugs that will benefit cancer patients undergoing targeted RT.

Modification of High LET Radiation-induced Damage and Its Repair in Yeast by Hypoxia

1979 ◽  
Vol 36 (5) ◽  
pp. 479-488 ◽  
Author(s):  
P. Subrahmanyam ◽  
B.S. Rao ◽  
N.M.S. Reddy ◽  
M.S.S. Murthy ◽  
U. Madhvanath
Keyword(s):  
High Let Radiation ◽  
High Let ◽  
Radiation Induced

Swift heavy ion irradiation of ZnO nanoparticles embedded in silica: Radiation-induced deoxidation and shape elongation

2013 ◽  
Vol 103 (20) ◽  
pp. 203106 ◽  
Author(s):  
H. Amekura ◽  
N. Okubo ◽  
N. Ishikawa ◽  
D. Tsuya ◽  
K. Mitsuishi ◽  
...  
Keyword(s):  
Zno Nanoparticles ◽  
Ion Irradiation ◽  
Heavy Ion ◽  
Swift Heavy Ion Irradiation ◽  
Heavy Ion Irradiation ◽  
Swift Heavy Ion ◽  
Radiation Induced

Effect of Cascade Remnants on Freely Migrating Defects in Cu -1 % Au Alloys

1995 ◽  
Vol 396 ◽  
Author(s):  
A. Iwase ◽  
L. E. Rehn ◽  
P. M. Baldo ◽  
L. Funk
Keyword(s):  
Heavy Ions ◽  
Ion Irradiation ◽  
Ion Beam ◽  
Heavy Ion ◽  
The Other ◽  
Inert Gas ◽  
Heavy Ion Irradiation ◽  
Simultaneous Irradiation ◽  
Radiation Induced ◽  
Cu Ions

AbstractThe effects of cascade remnants on Freely Migrating Defects (FMD) were studied by measuring Radiation-Induced Segregation (RIS) in Cu-l%Au at 400°C during simultaneous irradiation with 1.5-MeV He and (400-800)-keV heavy ions (Ne, Ar or Cu). The large RIS observed during 1.5-MeV He-only irradiation was dramatically suppressed under simultaneous heavy ion irradiation. For Cu simultaneous irradiation, the suppression disappeared immediately after the Cu irradiation ceased, while for simultaneous inert gas (Ne or Ar) irradiation, the suppression persisted after the ion beam was turned off. These results demonstrate that the displacement cascades created by heavy ions introduce additional annihilation sites, which reduce the steady-state FMD concentrations. As the cascade remnants produced by Cu ions are thermally unstable at 400°C, the RIS suppression occurs only during simultaneous irradiation. On the other hand, the inert gas atoms which accumulate in the specimen apparently stabilize the cascade remnants, allowing the suppression to persist.

High-LET Radiation-Induced Response of Microvessels in the Hippocampus

2010 ◽  
Vol 173 (4) ◽  
pp. 486-493 ◽  
Author(s):  
Xiao Wen Mao ◽  
Cecile J. Favre ◽  
John R. Fike ◽  
Lucie Kubinova ◽  
Ella Anderson ◽  
...  
Keyword(s):  
Induced Response ◽  
High Let Radiation ◽  
High Let ◽  
Radiation Induced
Sign in / Sign up

Export Citation Format

Share Document