Hematopoietic Cell Renewal as the Limiting Factor in Low-Level Radiation Exposure: Diagnostic Implications and Therapeutic Options

Fliedner, Theodor M.; Friesecke, Iris; Graessle, Dieter H.; Paulsen, Carola; Weiß, Melanie

doi:10.1093/milmed/167.suppl_1.46

Cited by 12 publications

(5 citation statements)

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“…ARS includes hematopoietic syndrome (1 Gy to 8 Gy), gastrointestinal syndrome (> 8 Gy) and cardiovascular/CNS syndrome (> 20 Gy) and follows well defined pathologies [ 5 , 6 ]. Acute radiation exposure in the range between 1 and 8 Gy leads to a drop in circulating blood cells [ 7 ]. At the higher end of this radiation dose range, blood cell counts continue to decline due to the demise of bone marrow stem/progenitor cells leading to lethality.…”

Section: Introductionmentioning

confidence: 99%

Administration of ON 01210.Na after exposure to ionizing radiation protects bone marrow cells by attenuating DNA damage response

et al. 2012

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BackgroundIonizing radiation-induced hematopoietic injury could occur either due to accidental exposure or due to diagnostic and therapeutic interventions. Currently there is no approved drug to mitigate radiation toxicity in hematopoietic cells. This study investigates the potential of ON 01210.Na, a chlorobenzylsulfone derivative, in ameliorating radiation-induced hematopoietic toxicity when administered after exposure to radiation. We also investigate the molecular mechanisms underlying this activity.MethodsMale C3H/HeN mice (n = 5 mice per group; 6-8 weeks old) were exposed to a sub-lethal dose (5 Gy) of γ radiation using a 137Cs source at a dose rate of 0.77 Gy/min. Two doses of ON 01210.Na (500 mg/kg body weight) were administered subcutaneously at 24 h and 36 h after radiation exposure. Mitigation of hematopoietic toxicity by ON 01210.Na was investigated by peripheral white blood cell (WBC) and platelet counts at 3, 7, 21, and 28 d after radiation exposure. Granulocyte macrophage colony forming unit (GM-CFU) assay was done using isolated bone marrow cells, and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) was performed on bone marrow sections at 7 d post-exposure. The DNA damage response pathway involving ataxia telangiectasia mutated (ATM) and p53 was investigated by Western blot in bone marrow cells at 7 d post-exposure.ResultsCompared to the vehicle, ON 01210.Na treated mice showed accelerated recovery of peripheral WBC and platelet counts. Post-irradiation treatment of mice with ON 01210.Na also resulted in higher GM-CFU counts. The mitigation effects were accompanied by attenuation of ATM-p53-dependent DNA damage response in the bone marrow cells of ON 01210.Na treated mice. Both phospho-ATM and phospho-p53 were significantly lower in the bone marrow cells of ON 01210.Na treated than in vehicle treated mice. Furthermore, the Bcl2:Bax ratio was higher in the drug treated mice than the vehicle treated groups.ConclusionsON 01210.Na treatment significantly mitigated the hematopoietic toxicity induced by a sub-lethal radiation dose. Mechanistically, attenuation of ATM-p53 mediated DNA damage response by ON 01210.Na is contributing to the mitigation of radiation-induced hematopoietic toxicity.

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Section: Introductionmentioning

confidence: 99%

Administration of ON 01210.Na after exposure to ionizing radiation protects bone marrow cells by attenuating DNA damage response

et al. 2012

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“…The 30-day survival assay showed that the combined administration of Sal and Ex-RAD provided significant protection to mice after 8 Gy irradiation. Acute radiation exposure leads to a drop in circulating blood cells and hemorrhage due to radiation-induced loss of platelets remains a life-threatening issue (22,23). In this initial investigation, we demonstrated that Sal and Ex-RAD significantly increased the peripheral WBC and platelet counts, mitigating radiation-induced hematopoietic toxicity.…”

Section: Discussionmentioning

confidence: 79%

Salidroside, a scavenger of ROS, enhances the radioprotective effect of Ex-RAD® via a p53-dependent apoptotic pathway

et al. 2017

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Salidroside (Sal), the predominant component of a Chinese medicinal herb, Rhodiola rosea L., has become an attractive bioagent due to its significant anti-radiation, antioxidant and immune adjustment effects. We explored the radioprotective effect of Sal to ascertain whether it could enhance the anti-radiation effect of ON 01210.Na (Ex-RAD®) in vivo and in vitro, and elucidate its underlying mechanism. Our data demonstrated that Sal inhibited radiation-induced apoptosis, scavenged reactive oxygen species (ROS), and decreased the DNA damage of human umbilical vein endothelial cells (HUVECs). Sal downregulated the expression of Bax and p53 and increased the ratio of Bcl-2/Bax, which indicated that Sal inhibited the radiation-induced apoptosis through p53-dependent pathways. The radioprotection of the Sal pretreatment was also evidenced by an increasing survival rate of the mice, maintaining antioxidant enzyme levels in the liver, and accelerating hematopoietic recovery. The results suggest that Sal exhibits an excellent radioprotective effect with powerful antioxidant activity in vitro and in vivo. Sal enhanced the radioprotective effect of Ex-RAD by improving the antioxidant effect, the scavenging of ROS, by accelerating hematopoietic recovery and DNA repair as well as by regulating apoptotic and repair signaling pathways. Combined modality treatments were more effective than single-agent treatments, demonstrating the value of multiple-agent radioprotectants.

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“…Hematopoietic syndrome may occur after exposure to significant radiation dose and all blood components may be affected adversely [8]. Blood being a vital special circulating tissue composed of cells suspended in a fluid (plasma) with a major function of maintaining homeostasis [9] may experience decline in cell count on exposure to ionizing radiation leading to drop in circulating blood cells which is detrimental to the health of the individual [10]. The white blood cells also called leukocytes are the mobile units of the body's protective system [11].…”

Section: Introductionmentioning

confidence: 99%

Effect of Low Dose (Diagnostic X-Rays) on Peripheral White Blood Cells Count in Guinea Pigs (Cavia porcellus)

Luntsi¹,

Daniel²,

Nwobi³

et al. 2019

Nuclear Medicine Physics

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Exposure to ionizing radiation is known to affect some hematological parameters of biological sample. This study was aimed at evaluating the effect of ionizing radiation within the diagnostic range on some hematological parameters in guinea pigs. Thirty six (36) apparently healthy adult guinea pigs of both sexes weighing between 700 and 1200 g were used. The guinea pigs were categorized in to three groups, 12 per group; group A (control), group B, and C were exposed to X-rays within the diagnostic range, using 70 kV and 12.5mAs; using X-ray machine MS-185, serial no. 0904 GE at a source to skin distance (SSD) of 90 cm. Blood samples were collected from all the guinea pigs at intervals of 1, 24, 72, 168 and 336 hours post-irradiation, and subjected to standard hematological analysis. A continuous decline in the mean total white blood cell count and mean lymphocyte, monocyte, neutrophil and eosinophil count after 1 hour in both groups was observed, and more pronounced after 24 hours post-irradiation. However, stability was observed 72 hours post-irradiation in both groups. In conclusion, a depleting effect of low dose ionizing radiation on white blood cell count was found, with appreciable recovery occurring after 72 hours onward.

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Hematopoietic Cell Renewal as the Limiting Factor in Low-Level Radiation Exposure: Diagnostic Implications and Therapeutic Options

Cited by 12 publications

References 0 publications

Administration of ON 01210.Na after exposure to ionizing radiation protects bone marrow cells by attenuating DNA damage response

Administration of ON 01210.Na after exposure to ionizing radiation protects bone marrow cells by attenuating DNA damage response

Salidroside, a scavenger of ROS, enhances the radioprotective effect of Ex-RAD® via a p53-dependent apoptotic pathway

Effect of Low Dose (Diagnostic X-Rays) on Peripheral White Blood Cells Count in Guinea Pigs (Cavia porcellus)

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