scholarly journals KR-31831 improves survival and protects hematopoietic cells and radiosensitive tissues against radiation-induced injuries in mice

2021 ◽  
pp. 112350
Author(s):  
Jeong Hyun Lee ◽  
Hyuna Yi ◽  
Ju Hee Lee ◽  
Ho Won Seo ◽  
Kwang-Seok Oh ◽  
...  
Blood ◽  
2000 ◽  
Vol 95 (8) ◽  
pp. 2645-2650 ◽  
Author(s):  
Lisa A. Porter ◽  
Gurmit Singh ◽  
Jonathan M. Lee

Abstract γ-Radiation is a potent inducer of apoptosis. There are multiple pathways regulating DNA damage-induced apoptosis, and we set out to identify novel mechanisms regulating γ-radiation–induced apoptosis in hematopoietic cells. In this report, we present data implicating the cyclin B1 protein as a regulator of apoptotic fate following DNA damage. Cyclin B1 is the regulatory subunit of the cdc2 serine/threonine kinase, and accumulation of cyclin B1 in late G2 phase of the cell cycle is a prerequisite for mitotic initiation in mammalian cells. We find that abundance of the cyclin B1 protein rapidly increases in several mouse and human hematopoietic cells (Ramos, DP16, HL60, thymocytes) undergoing γ-radiation–induced apoptosis. Cyclin B1 accumulation occurs in all phases of the cell cycle. Antisense inhibition of cyclin B1 accumulation decreases apoptosis, and ectopic cyclin B1 expression is sufficient to induce apoptosis. These observations are consistent with the idea that cyclin B1 is both necessary and sufficient for γ-radiation-induced apoptosis.


Blood ◽  
2021 ◽  
Author(s):  
Tao Cheng ◽  
Linping Hu ◽  
Xiuxiu Yin ◽  
Yawen Zhang ◽  
Aiming Pang ◽  
...  

Total body irradiation (TBI) is commonly used in host conditioning regimens for human hematopoietic stem cell (HSC) transplantation to treat various hematological disorders. Exposure to TBI not only induces acute myelosuppression and immunosuppression but also impairs the various components of the HSC niche in recipients. Our previous study demonstrated that radiation-induced bystander effects (RIBE) of irradiated recipients decreased the long-term repopulating ability of transplanted mouse HSCs. However, RIBE on human HSCs have not been studied. Here, we report that RIBE on transplanted human hematopoietic cells impaired the long-term hematopoietic reconstitution of human HSCs as well as the colony-forming ability of human hematopoietic progenitor cells (HPCs). Our further studies found that the RIBE-affected human hematopoietic cells showed enhanced DNA damage responses, cell cycle arrest and p53-dependent apoptosis, mainly due to oxidative stress. Moreover, multiple antioxidants could mitigate these bystander effects, though at different efficacies both in vitro and in vivo. Taken together, these findings suggest that RIBE impairs human HSCs by oxidative DNA damage. This study provides definitive evidence for RIBE in transplanted human HSCs and further justifies the necessity for conducting clinical trials to assess the ability of multiple antioxidants to improve the efficacy of HSC transplantation for patients with hematological or non-hematological disorders.


2017 ◽  
Vol 187 (3) ◽  
pp. 382 ◽  
Author(s):  
Fei Xu ◽  
Xin Li ◽  
Lili Yan ◽  
Na Yuan ◽  
Yixuan Fang ◽  
...  

PLoS ONE ◽  
2019 ◽  
Vol 14 (4) ◽  
pp. e0205626 ◽  
Author(s):  
Desirée Bartolini ◽  
Yanzhong Wang ◽  
Jie Zhang ◽  
Daniela Giustarini ◽  
Ranieri Rossi ◽  
...  

2003 ◽  
Vol 5 (12) ◽  
pp. 1028-1038 ◽  
Author(s):  
Alain Chapel ◽  
Jean Marc Bertho ◽  
Morad Bensidhoum ◽  
Loic Fouillard ◽  
Randell G. Young ◽  
...  

Blood ◽  
2000 ◽  
Vol 95 (8) ◽  
pp. 2645-2650 ◽  
Author(s):  
Lisa A. Porter ◽  
Gurmit Singh ◽  
Jonathan M. Lee

γ-Radiation is a potent inducer of apoptosis. There are multiple pathways regulating DNA damage-induced apoptosis, and we set out to identify novel mechanisms regulating γ-radiation–induced apoptosis in hematopoietic cells. In this report, we present data implicating the cyclin B1 protein as a regulator of apoptotic fate following DNA damage. Cyclin B1 is the regulatory subunit of the cdc2 serine/threonine kinase, and accumulation of cyclin B1 in late G2 phase of the cell cycle is a prerequisite for mitotic initiation in mammalian cells. We find that abundance of the cyclin B1 protein rapidly increases in several mouse and human hematopoietic cells (Ramos, DP16, HL60, thymocytes) undergoing γ-radiation–induced apoptosis. Cyclin B1 accumulation occurs in all phases of the cell cycle. Antisense inhibition of cyclin B1 accumulation decreases apoptosis, and ectopic cyclin B1 expression is sufficient to induce apoptosis. These observations are consistent with the idea that cyclin B1 is both necessary and sufficient for γ-radiation-induced apoptosis.


1998 ◽  
Vol 4 (S2) ◽  
pp. 1078-1079
Author(s):  
D.W. Wang ◽  
R.Y. Peng ◽  
C.Q. Xiong

There have rarely been reported on radiation induced hematopoietic cells apoptosis and the recovery ,the expression and significance of oncogenes, tumor suppresser genes, hematopoietic grouth factors and their receptors in bone marrow.By meams of routine pathology, specific stainning, electron microscope, immunocytochemistry, image analysis, in situ hybridization, in situ terminal end labelling, in situ PCR and DNA electrophoresis, The machanisms of hematopoietic cells apoptosis and then recovery in mouse bone marrow were studies through LAC A mouse total body irradiation with 60Co γ -rays.The results showed: The bone marrow in each radiated group appeared obvious injury and then recovery, and the lessions were the most typical in 5.5Gy irradiation group, the pathologic changes were divided into four phases: namely the phase of hematopoietic cells apoptosis,bone marrow at 6hours after radiation. Furthermore, the higher radiation dose, the more the apoptotic cells were(table l).


Author(s):  
T. Mukai ◽  
T. E. Mitchell

Radiation-induced homogeneous precipitation in Ni-Be alloys was recently observed by high voltage electron microscopy. A coupling of interstitial flux with solute Be atoms is responsible for the precipitation. The present investigation further shows that precipitation is also induced at thin foil surfaces by electron irradiation under a high vacuum.


Author(s):  
Robert C. Rau ◽  
John Moteff

Transmission electron microscopy has been used to study the thermal annealing of radiation induced defect clusters in polycrystalline tungsten. Specimens were taken from cylindrical tensile bars which had been irradiated to a fast (E > 1 MeV) neutron fluence of 4.2 × 1019 n/cm2 at 70°C, annealed for one hour at various temperatures in argon, and tensile tested at 240°C in helium. Foils from both the unstressed button heads and the reduced areas near the fracture were examined.Figure 1 shows typical microstructures in button head foils. In the unannealed condition, Fig. 1(a), a dispersion of fine dot clusters was present. Annealing at 435°C, Fig. 1(b), produced an apparent slight decrease in cluster concentration, but annealing at 740°C, Fig. 1(C), resulted in a noticeable densification of the clusters. Finally, annealing at 900°C and 1040°C, Figs. 1(d) and (e), caused a definite decrease in cluster concentration and led to the formation of resolvable dislocation loops.


Author(s):  
M. L. Knotek

Modern surface analysis is based largely upon the use of ionizing radiation to probe the electronic and atomic structure of the surfaces physical and chemical makeup. In many of these studies the ionizing radiation used as the primary probe is found to induce changes in the structure and makeup of the surface, especially when electrons are employed. A number of techniques employ the phenomenon of radiation induced desorption as a means of probing the nature of the surface bond. These include Electron- and Photon-Stimulated Desorption (ESD and PSD) which measure desorbed ionic and neutral species as they leave the surface after the surface has been excited by some incident ionizing particle. There has recently been a great deal of activity in determining the relationship between the nature of chemical bonding and its susceptibility to radiation damage.


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