scholarly journals ASSESSMENT OF RADIOPROTECTIVE ACTION OF BASIDIOMYCOTIC MELANIN PIGMENTS ON THE HEMATOPOIETIC SYSTEM OF Balb/C MICE UNDER EXPOSURE TO IONIZING RADIATION IN SUBLETHAL DOSE

2019 ◽  
Vol 24 ◽  
pp. 210-219
Author(s):  
D. Bilko ◽  
◽  
I. Russu ◽  
N. Bilko ◽  
◽  
...  
Keyword(s):  
Ionizing Radiation ◽  
Sublethal Dose ◽  
Hematopoietic System ◽  
Radioprotective Action

Induction of Hematopoietic Stem Cell Senescence by Ionizing Radiation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1362-1362
Author(s):  
Yong Wang ◽  
Bradley A. Schulte ◽  
Amanda C. LaRue ◽  
Makio Ogawa ◽  
Daohong Zhou
Keyword(s):  
Stem Cell ◽  
Ionizing Radiation ◽  
Hematopoietic Stem Cell ◽  
Cellular Senescence ◽  
Molecular Mechanisms ◽  
Chemotherapeutic Agents ◽  
Sublethal Dose ◽  
Self Renewal ◽  
Hematopoietic Stem

Abstract Exposure to ionizing radiation (IR) and certain chemotherapeutic agents not only causes acute bone marrow (BM) suppression but also leads to long-term residual hematopoietic injury. This later effect has been attributed to the damage to hematopoietic stem cell (HSC) self-renewal. Using a mouse model, we investigated whether IR induces senescence in HSCs, as induction of HSC senescence can lead to the impairment of HSC self-renewal. The results showed that exposure of C57BL/6 mice to a sublethal dose (6.5 Gy) of total body irradiation (TBI) resulted in a long-lasting quantitative and qualitative reduction in HSCs (Lin− c-kit+ Sca-1+ or LKS+ cells). Compared to control HSCs, HSCs from irradiated BM at 4 weeks after TBI exhibited a significant reduction in day-35 CAFC frequency and deficiency in cell proliferation and colony formation in a single cell culture assay stimulated with SCF/TPO and SCF/TPO/IL-3, respectively. In addition, transplantation of irradiated HSCs (500 LKS+ cells/recipient) produced less than 1% long-term (2-month) engraftment in a competitive repopulation assay while transplantation of the same number of control HSCs resulted in 24.8% engraftment. Furthermore, HSCs from irradiated mice expressed increased levels of p16Ink4a and senescence-associated beta-galactosidase (SA-beta-gal), two commonly used biomarkers of cellular senescence. In contrast, hematopoietic progenitor cells (Lin− c-kit+ Sca-1− or LKS− cells) from irradiated mice did not show significant changes in clonogenesity in a CFU assay and expressed minimal levels of p16Ink4a and SA-beta-gal. These results suggest that exposure to IR can induce senescence selectively in HSCs but not in HPCs. Interestingly, this IR- induced HSC senescence was associated with a prolonged elevation of p21Cip1/Waf1, p16Ink4a and p19ARF mRNA expression, whereas the expression of p27Kip1, p18Ink4c and p19 Ink4d mRNA was not increased. This suggests that p21Cip1/Waf1, p16Ink4a and p19ARF may play an important role in IR-induced senescence in HSCs, since their expression has been implicated in the initiation, establishment and maintenance of cellular senescence. Therefore, these findings provide valuable insights into the mechanisms underlying IR-induced long-term BM damage. This could lead to the discovery of novel molecular targets for intervention to circumvent IR-induced BM toxicity. In addition, understanding how normal HSCs senesce after IR and chemotherapy will help us to elucidate the molecular mechanisms whereby leukemia/cancer stem cells evade these cancer treatments and provide better knowledge of organismal aging.

Inhibition of p38 MAPK Reduces Ionizing Radiation-Induced Hematopoietic Cell Injury.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4181-4181
Author(s):  
Lingbo Liu ◽  
Daohong Zhou ◽  
Yong Wang
Keyword(s):  
Ionizing Radiation ◽  
P38 Mapk ◽  
Cellular Senescence ◽  
Mapk Pathway ◽  
Hematopoietic Cells ◽  
Hematopoietic Cell ◽  
Sublethal Dose ◽  
Hematopoietic Stem ◽  
P38 Mapk Pathway

Abstract Our previous studies demonstrated that exposure to ionizing radiation (IR) causes long-term bone marrow (BM) damage by induction cellular senescence in hematopoietic cells. The senescent hematopoietic cells exhibited an elevated activity of the senescence associated β-galactosidase (SA-β-gal), a biomaker for senescent cells, and expressed increased levels of p16Ink4a (p16), whose expression has been implicated in the establishment and maintenance of cellular senescence. Activation of the p38 MAPK pathway has been implicated in the induction of cell cycle arrest and senescence in response to a variety of stressors in part by up-regulating the expression of p16. Therefore, in the present study we examined the role of the p38 MAPK pathway in IR-induced hematopoietic cell senescence. The results showed that exposure of male C57BL/6 mice to a sublethal dose (6.5 Gy) of total body irradiation (TBI) caused a sustained activation (>4 weeks) of p38 in Lin− c-kit+ Sca-1+ (LKS+) hematopoietic stem cells (HSCs). This activation was associated with a persistent up-regulation of p16 and quantitative and qualitative reduction of LKS+ HSCs. Inhibition of p38 activity with SB202190 (a specific p38 inhibitor) attenuated IR-induced inhibition of the hematopoietic function of BM hematopoietic cells in an in vitro colony forming cell (CFC) assay. Moreover, the production of hematopoietic progenitor cells (HPCs) in SB202190-treated BM cells was 7.5 fold higher than that of irradiated cells without SB202190 treatment after five weeks of long-term BM cell culture (LTBMC); and the cells treated with SB202190 after IR retained their clonogenic function while the control irradiated cells lose their ability to form colonies. These findings suggest that p38 may play an important role in mediating IR-induced suppression of hematopoietic cell function and pharmacological inhibition of the p38 pathway may potentially be developed as novel therapeutic strategy to ameliorate IR- and chemotherapy-induced BM toxicity.

Ionizing Radiation Induces Hematopoietic Stem Cell Senescence and Long-Term Bone Marrow Suppression in a p16Ink4a/Arf-Independent manner

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1345-1345
Author(s):  
Lijian Shao ◽  
Wei Feng ◽  
Hongliang Li ◽  
Yong Wang ◽  
Norman Sharpless ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Ionizing Radiation ◽  
Hematopoietic Stem Cell ◽  
Molecular Mechanisms ◽  
Conflicts Of Interest ◽  
Sublethal Dose ◽  
Independent Manner ◽  
Hematopoietic Stem

Abstract Abstract 1345 Many patients receiving chemotherapy and/or ionizing radiation (IR) develop residual (or long-term) bone marrow (BM) injury that can not only limit the success of cancer treatment but also adversely affect their quality of life. Although residual BM injury has been largely attributed to the induction of hematopoietic stem cell (HSC) senescence, neither the molecular mechanisms by which chemotherapy and/or IR induce HSC senescence have been clearly defined, nor has an effective treatment been developed to ameliorate the injury. The Ink4a-Arf locus encodes two important tumor suppressors, p16Ink4a (p16) and Arf. Both of them have been implicated in mediating the induction of cellular senscence in a variety of cells including HSCs. Therefore, we examined the role of p16 and/or Arf in IR-induced HSC senescence and long-term BM suppression using a total body irradiation (TBI) mouse model. The results from our studies show that exposure of wild-type (WT) mice to a sublethal dose (6 Gy) of TBI induces HSC senescence and long-term BM suppression. The induction of HSC senescence is not associated with a reduction in telemore length in HSCs and their progeny, but is associated with significant increases in the production of reactive oxygen species (ROS), the expression of p16 and Arf mRNA, and the activity of senescence-associated β-galacotosidase (SA-β-gal) in HSCs. However, genetical deletion of Ink4a and/or Arf has no effect on TBI-induced HSC senescence, as HSCs from the Ink4a and/or Arf knockout mice after exposure to TBI exhibit similar changes as those seen in the cells from irradiated WT mice in comparison with the cells from un-irradiated mice with correspondent genotypes. In addition, TBI-induced long-term BM suppression is also not attenuated by the deletion of the Ink4a and/or Arf genes. These findings suggest that IR induces HSC senescence and long-term BM suppression in a p16Ink4a/Arf-independent manner. Disclosures: No relevant conflicts of interest to declare.

scholarly journals MODELING DETERMINISTIC EFFECTS IN HEMATOPOIETIC SYSTEM CAUSED BY CHRONIC EXPOSURE TO IONIZING RADIATION IN LARGE HUMAN COHORTS

2010 ◽  
Vol 99 (3) ◽  
pp. 322-329 ◽  
Author(s):  
Igor V. Akushevich ◽  
Galina A. Veremeyeva ◽  
Georgy P. Dimov ◽  
Svetlana V. Ukraintseva ◽  
Konstantin G. Arbeev ◽  
...  
Keyword(s):  
Ionizing Radiation ◽  
Chronic Exposure ◽  
Hematopoietic System

Compromised hematopoiesis and increased DNA damage following non-lethal ionizing radiation of a human hematopoietic system reconstituted in immunodeficient mice

2015 ◽  
Vol 91 (8) ◽  
pp. 687-687
Author(s):  
Changshan Wang ◽  
Shunsuke Nakamura ◽  
Motohiko Oshima ◽  
Makiko Mochizuki-Kashio ◽  
Yaeko Nakajima-Takagi ◽  
...  
Keyword(s):  
Dna Damage ◽  
Ionizing Radiation ◽  
Hematopoietic System ◽  
Immunodeficient Mice

scholarly journals Inter-Strain Differences in LINE-1 DNA Methylation in the Mouse Hematopoietic System in Response to Exposure to Ionizing Radiation

2017 ◽  
Vol 18 (7) ◽  
pp. 1430 ◽  
Author(s):  
Isabelle Miousse ◽  
Jianhui Chang ◽  
Lijian Shao ◽  
Rupak Pathak ◽  
Étienne Nzabarushimana ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Ionizing Radiation ◽  
Strain Differences ◽  
Hematopoietic System

scholarly journals A New Model of Short- and Long-term Effects of Exposure to Ionizing Radiation in Hematopoietic System of Human

2008 ◽  
Vol 43 (5) ◽  
Author(s):  
I. Akushevich ◽  
G. Veremeyeva ◽  
S. Ukraintseva ◽  
K. Arbeev ◽  
A. Akleyev ◽  
...  
Keyword(s):  
Ionizing Radiation ◽  
Long Term Effects ◽  
Hematopoietic System ◽  
New Model ◽  
Short And Long Term

scholarly journals Evaluation of Lipid Peroxidation under Immobilization Stress in Irradiated Animals in Experiment

2021 ◽  
Vol 9 (A) ◽  
Author(s):  
Assem K. Okassova ◽  
Oralbek Z. Ilderbayev ◽  
Akmaral Zh. Nursafina ◽  
Gulmira M. Zharmakhanova ◽  
Bibigul B. Rakhimova ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Free Radical ◽  
Ionizing Radiation ◽  
Gamma Radiation ◽  
Immobilization Stress ◽  
Free Radical Oxidation ◽  
Sublethal Dose ◽  
Combined Effects ◽  
Radical Oxidation

BACKGROUND: For many years, the world community has been concerned with the problem of the consequences of radiation exposure on the human body. A wide range of possible variants of radiation effects on humans and biota determines the range of necessary pharmacological means of protecting the organism and populations. In the mechanisms of the formation of radioresistance, the leading role is assigned to the processes of lipid peroxidation (LPO) and the antioxidant (AO) system. The study of the effect of such factors as radiation and immobilization stress on the body separately and in combination is relevant since the modern conditions of human habitation are characterized by high urbanization, physical inactivity, and a complex radioecological situation in a number of regions. AIM: The aim of the study was to study the role of free radical oxidation in the tissues of the adrenal glands and immunocompetent organs and cells under the combined effect of a sublethal dose of gamma radiation and immobilization stress in the experiment. MATERIALS AND METHODS: The work was carried out on 40 male Wistar rats: I-control; II-subjected to immobilization stress after 1 h; III-exposed to gamma irradiation; and IV-tested combined effects (immobilization stress and gamma radiation). Before the exposure, there was topometric-dosimetric preparation of the experimental animals. To this end, the object was placed on an isocentric therapeutic desk of Terasix X-ray simulator (Czech Republic), which is similar to the therapeutic desk of the γ-irradiator by its construction and parameters. RESULTS: The results obtained make it possible to assess the role of free radical oxidation under the combined action of ionizing radiation at a sublethal dose and immobilization stress in the experiment. The combined effect was accompanied by the accumulation of diene conjugates and malondialdehyde products in homogenates and the development of double oxidative stress in the test objects. The dominant role of ionizing radiation was revealed under the combined effects of immobilization stress and radiation factor. CONCLUSIONS: In animals of the 4th group, the state of oxidative-metabolic processes was characterized by overproduction of LPO products and subsequently by depression of AO defense. The urgency of continuing research on the combined effects of radiation and stress factors on public health and taking measures to eliminate negative effects on the population seems to be undoubted.

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