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ABSTRACT: Allogeneic hematopoietic stem cell transplantation is a potentially curative therapy for many malignant and nonmalignant hematologic diseases. However, acute graft-versus-host disease (aGVHD) is a lethal complication of hematopoietic stem cell transplantation, which limits its application. Cytokines such as tumor necrosis factor-α and interleukin-6 play an extremely important role in the formation and development of aGVHD. Reactive oxygen species, such as hydroxyl radicals, also play an important role in the formation and development of aGVHD. In recent years, hydrogen was reported to have an ability to inhibit the levels of cytokines, such as tumor necrosis factor and interleukin-6 in vivo, and it also has a strong selective free radical-scavenging ability. Therefore, we hypothesized that hydrogen may have therapeutic effects on aGVHD.
To determine whether hydrogen could protect mice from lethal GVHD in a major histocompatibility complex-incompatible murine bone marrow transplantation (BMT) model, survival rates of mice were calculated and leukocyte counts were also determined after BMT. We also examined serum cytokine levels and scored clinical signs of GVHD mice after BMT.
This article demonstrated that the administration of hydrogen-rich saline increased the survival rate and clinical score of aGVHD mice. Administration of hydrogen-rich saline after transplantation also promoted the recovery of white blood cells of aGVHD mice. However, there was no report on the therapeutic effects of hydrogen on aGVHD. It is suggested that hydrogen has a potential as an effective and safe therapeutic agent on aGVHD.
Transplantation 03/2013; 95(5):658-62. · 4.00 Impact Factor
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ABSTRACT: Abstract It has been reported that carboxyfullerene (C3) exhibits a strong free radical scavenging capacity, which plays a critical role in radiation damage. We hypothesized that C3 is an effective radioprotective agent. In this study, we demonstrated that C3 effectively scavenged hydroxyl radical in a cell-free Fenton system and C3 showed no obvious toxicity for cultured cells. Different concentrations (100-400mg/L) of C3 pretreatment effectively protected AHH-1 cells from radiation-induced apoptosis, by about 2 folds, while only 100mg/L C3 reduced apoptosis rate of HIEC cells. C3 also alleviated DNA damage detected by comet assay at 0, 4 and 8h after irradiation. It was found that 75% mice were protected from 7.2Gy γ-irradiation induced death when 100mg/kg C3 was administered prior to irradiation, but no change was observed for the survival time of mice who died. We also found that C3 attenuated radiation-mediated decreases in endogenous antioxidants such as SOD and GSH and reduced the level of MDA. In conclusion, these data showed that C3 effectively protected cells and mice from radiation injury, thus indicating the potential of C3 as a safe and effective radioprotectant.
Free radical research 01/2013; · 2.22 Impact Factor
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ABSTRACT: Abstract Background: Radiation therapy produced unwanted side effect on normal tissues, such as radiodermatitis. Hydrogen was previously shown capable of radiation protective in both animals and cell cultures. The effect of hydrogen was now to be investigated on radiation-induced cutaneous. Objective: Development of dermatitis is a frequent side effect of radiotherapy of patients with head-and-neck cancer. Here we analyzed the radioprotective efficacy of hydrogen under conditions of local, single dose or fractionated radiation treatment, and its possible molecular mechanisms. Methods: Mice received either single-dose or fractioned irradiation of the head-and-neck area with or without subcutaneous injection of hydrogen solution before irradiation. In vitro, the effect of hydrogen medium on radiation-induced cell viability , apoptosis and biochemical assays was measured. Result: hydrogen significantly reduced the severity of dermatitis, accelerated tissue recovery, and reduced the extent of radiation induced weight loss in mice after a single dose of 15 or 20 Gy but not 25 Gy of radiation. Hydrogen was also protective from cumulative doses of 30 Gy delivered in three fractions, respectively. Hydrogen also protect HaCaT cells from radiation-induced injury, it could significantly inhibit ionizing injury. Conclusion: These results suggest that hydrogen has a positive effect on acute radiodermatitis.
Journal of Dermatological Treatment 12/2012; · 1.23 Impact Factor
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Cong Liu,
Chuanfeng Zhou,
Fu Gao,
Shengyun Cai,
Chao Zhang,
Luqian Zhao,
Fang Zhao,
Fei Cao,
Jing Lin,
Yanyong Yang,
Jin Ni,
Jun Jia,
Wei Wu,
Li Zhou,
Jianguo Cui,
Wei Zhang,
Bailong Li, Jianming Cai
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ABSTRACT: Due to the intrinsic resistance of many tumors to radiotherapy, current methods to improve the survival of cancer patients largely depend on increasing tumor radiosensitivity. It is well-known that miR-200c inhibits epithelial-mesenchymal transition (EMT), and enhances cancer cell chemosensitivity. We sought to clarify the effects of miR-200c on the radiosensitization of human breast cancer cells. In this study, we found that low levels of miR-200c expression correlated with radiotolerance in breast cancer cells. MiR-200c overexpression could increase radiosensitivity in breast cancer cells by inhibiting cell proliferation, and by increasing apoptosis and DNA double-strand breaks. Additionally, we found that miR-200c directly targeted TANK-binding kinase 1 (TBK1). However, overexpression of TBK1 partially rescued miR-200c mediated apoptosis induced by ionizing radiation. In summary, miR-200c can be a potential target for enhancing the effect of radiation treatment on breast cancer cells. J. Cell. Biochem. © 2012 Wiley Periodicals, Inc.
Journal of Cellular Biochemistry 09/2012; · 2.87 Impact Factor
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ABSTRACT: Aplastic anemia (AA) is a rare bone marrow failure disorder with high mortality rate, which is characterized by pancytopenia and an associated increase in the risk of hemorrhage, infection, organ dysfunction and death. The oxidation phenomenon and/or the formation of free radicals have been suggested to be causally related to various hematological disorders, including aplastic anemia. TNF-α, IL-6, and IL-2 also play important roles in the pathogenesis of AA. Recent studies have provided evidence that hydrogen inhalation can selectively reduce cytotoxic oxygen radicals and exert antioxidant effects. It was also reported that hydrogen could suppress the levels of TNF-α and IL-6. Based on these findings, we hypothesize that hydrogen therapy may be an effective, simple, economic and novel strategy in the treatment of aplastic anemia.
Medical science monitor: international medical journal of experimental and clinical research 06/2012; 18(6):HY19-22. · 1.70 Impact Factor
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ABSTRACT: Molecular hydrogen (dihydrogen, H(2)) acts as a therapeutic antioxidant by selectively reducing hydroxyl radicals (•OH) and peroxynitrite (ONOO-). It has been well-known that ionising radiation (IR) causes oxidative damage and consequent apoptosis mainly due to the production of •OH that follows radiolysis of H(2)O. Our department reported the protective effect of H(2) in irradiated cells and mice for the first time, and this effect is well repeated by us and another laboratory in different experimental animal models. A randomised, placebo-controlled investigation also showed consumption of H(2) can improve the quality of life of patients treated with radiotherapy for liver tumours. These encouraging results suggested that H(2) has a potential as a radioprotective agent with efficacy and non-toxicity.
Free radical research 04/2012; 46(9):1061-7. · 2.22 Impact Factor
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ABSTRACT: There is growing evidence in recent years that the pristine fullerene may be endowed with strong pro-oxidant capacity to biological
samples. In this investigation we tested the hypothesis that water-soluble fullerene-C60 (nano-C60) may interact with ionizing radiation enhancing its antiproliferative effects. The two tumor cell lines with different radiosensitivity
B16 and SMMU-7721 were treated by a combination of pristine fullerene and 60Co γ irradiation. We measured cell survival rates, apoptotic characteristics, reactive oxygen species (ROS) production and
alteration of cell diameter with or without γ-irradiation. There was reduced survival with B16 and SMMU-7721 cells exposed
to nano-C60, with the inhibitory concentrations reducing the viability by 50% to 65 part per billion (ppb) and 150ppb respectively.
For cells exposed to nano-C60 prior to γ-irradiation, damage to cell membranes and increased numbers of apoptotic cells were detected by morphologic Hoechst-staining
analysis and Annexin V/propidium iodide double-staining. In cells exposed to nano-C60, there were increased levels of ROS, as measured by fluorescence detection under laser confocal microscopy. Preincubation
with non-toxic pristine C60 before γ-ray caused enlargement of cells with increased diameter. The results show that nano-C60 inhibits the growth of tumor cells at certain concentrations and increases the effects of 60Co γ-irradiation, possibly through the elevated production of cellular ROS and the membrane disruption. Data in this study
indicates a possible consideration of using C60 as a candidate of sensitization modifier in tumor radiation biology.
Journal of Nanoparticle Research 04/2012; 10(4):643-651. · 3.29 Impact Factor
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Yanyong Yang,
Bailong Li,
Cong Liu,
Yunhai Chuai,
Jixiao Lei,
Fu Gao,
Jianguo Cui,
Ding Sun,
Ying Cheng,
Chuanfeng Zhou, Jianming Cai
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ABSTRACT: Radiation often causes depletion of immunocytes in tissues and blood, which results in immunosuppression. Molecular hydrogen (H2) has been shown in recent studies to have potential as a safe and effective radioprotective agent through scavenging free radicals. This study was designed to test the hypothesis that H2 could protect immunocytes from ionizing radiation (IR).
H2 was dissolved in physiological saline or medium using an apparatus produced by our department. A 2-[6-(4'-hydroxy) phenoxy-3H-xanthen-3-on-9-yl] benzoate (HPF) probe was used to detect intracellular hydroxyl radicals (•OH). Cell apoptosis was evaluated by annexin V-FITC and Propidium iodide (PI) staining as well as the caspase 3 activity. Finally, we examined the hematological changes using an automatic Sysmex XE 2100 hematology analyzer.
We demonstrated H2-rich medium pretreatment reduced •OH level in AHH-1 cells. We also showed H2 reduced radiation-induced apoptosis in thymocytes and splenocytes in living mice. Radiation-induced caspase 3 activation was also attenuated by H2 treatment. Finally, we found that H2 rescued the radiation-caused depletion of white blood cells (WBC) and platelets (PLT).
This study suggests that H2 protected the immune system and alleviated the hematological injury induced by IR.
Medical science monitor: international medical journal of experimental and clinical research 04/2012; 18(4):BR144-8. · 1.70 Impact Factor
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ABSTRACT: Recent studies suggest that mangiferin aglycone (norathyriol) has great potential as a novel radioprotector without any known toxic side effects. In this study, we assessed the protective effects of mangiferin aglycone against radiation-induced injuries on normal human intestinal epithelial cells (HIECs), while using mangiferin as a reference compound. The in vitro experiments showed that pretreatment of either mangiferin aglycone or mangiferin could inhibit cytotoxic effects of ionizing irradiation (IR) on HIECs. Cellular changes were estimated by measuring cell viability, clonogenic surviving rate, and apoptotic rate. Compared to mangiferin, we found mangiferin aglycone had greater radioprotective effects of mangiferin aglycone on HIECs. It has been demonstrated that the cytotoxicity of ionizing radiation relates to its capacity to induce DNA damage. In view of this, we monitored DNA double-strand breaks (DSBs) using γH2AX foci formation to test whether mangiferin aglycone and mangiferin could modulate genotoxic effects of radiation. It shows that mangiferin aglycone could eliminate 46.8% of the total DSBs of the cells exposed to 2 Gy IR, which is significantly better than mangiferin. Complementing earlier results from our group, it appears possible to conclude that mangiferin aglycone presents potential useful effects on IR-induced damage and may be a better radioprotective agent than mangiferin therapeutically.
Journal of Cellular Biochemistry 03/2012; 113(8):2633-42. · 2.87 Impact Factor
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Yunhai Chuai,
Jianliang Shen,
Liren Qian,
Yicun Wang,
Yuecheng Huang,
Fu Gao,
Jianguo Cui,
Jin Ni,
Luqian Zhao,
Shulin Liu,
Xuejun Sun,
Bailong Li, Jianming Cai
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ABSTRACT: Recent studies show that molecular hydrogen (dihydrogen, H2) has potential as an effective and safe radioprotective agent through reducing oxidative stress. The aim of this study was to investigate whether H2 is able to protect spermatogenesis and hematopoiesis from radiation-induced injuries.
H2 was dissolved in physiological saline using an apparatus produced by our department. -60Co-gamma rays in the irradiation centre were used for irradiation. Spermatid head counts and histological analysis were used to evaluate spermatogenesis. Endogenous hematopoietic spleen colony formation (endoCFUs), bone marrow nucleated cells (BMNC) and peripheral blood (PB) leukocytes were used to evaluate hemopoiesis.
This study demonstrates that treating mice with H2 before ionizing radiation (IR) can increase the spermatid head count and protect seminiferous epithelium from IR. This study also demonstrates that H2 could significantly increase the number of endoCFUs, BMNC and PB leukocyte.
This study suggests that hydrogen-rich saline could partially protect spermatogenesis and hematopoiesis in irradiated mice.
Medical science monitor: international medical journal of experimental and clinical research 02/2012; 18(3):BR89-94. · 1.70 Impact Factor
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ABSTRACT: Our recent studies suggest that H2 (hydrogen) has a potential as a novel radioprotector without known toxic side effects. The present study was designed to examine the underlying radioprotective mechanism of H2 and its protective role on irradiated germ cells. Produced by the Fenton reaction and radiolysis of H2O, hydroxyl radicals (•OH) were identified as the free radical species that were reduced by H2. We used a H2 microelectrode to dynamically detect H2 concentration in vivo, and found H2 significantly reduced in situ fluorescence intensity of hydroxyphenyl fluorescein; however, as we treated the mice with H2 after irradiation, the decrease is not significant. We found that pre-treatment of H2 to IR (ionizing radiation) significantly suppressed the reaction of •OH and the cellular macromolecules which caused lipid peroxidation, protein carbonyl and oxidatively damaged DNA. The radioprotective effect of H2 on male germ cells was supported by ameliorated apoptotic findings examined by morphological changes and TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling) in testicular tissue, and by preserved viability of stem spermatogonia examined for testicular histological parameters, daily sperm production and sperm quality; we used WR-2721 [S-2-(3-aminopropylamino)ethyl phosphorothioic acid] as a reference compound. Our results represent the first in vivo evidence in support of a radioprotective role of H2 by neutralizing •OH in irradiated tissue with no side effects.
Biochemical Journal 11/2011; 442(1):49-56. · 4.90 Impact Factor
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ABSTRACT: Dendritic cells (DC) and myeloid-derived suppressor cells (MDSC) are important cells involved in immune response. DC can be generated from mouse bone marrow (BM) in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4. Recent studies have revealed that combined treatment of bone marrow MDSC with LPS plus IFN-γ inhibited the DC development but enhanced MDSC functions, such as NO release and T cell suppression. In our study, bone marrow precursor cells cultures in GM-CSF and IL-4 were treated with poly(I:C) through the culture, Gr1(+)CD11b(+) cells with MDSC functions, such as NO release and T cell suppression were accumulated in the culture system. Then the similar phenomenon was observed in the vesicular stomatitis virus infection in vivo. In conclusion, we demonstrated that the bone marrow precursor cells in the presence of GM-CSF and IL-4 can differentiate into MDSC, which is dependent on the dynamic of interaction with poly(I:C).
Molecular and Cellular Biochemistry 07/2011; 358(1-2):317-23. · 2.06 Impact Factor
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ABSTRACT: Radiotherapy is an important modality of cancer treatment. Radiation pneumonitis is a major obstacle to increasing the radiation dose in radiotherapy, and it is important to prevent this radiation-induced complication. Recent studies show that hydrogen has a potential as an effective and safe radioprotective agent by selectively reducing hydroxyl and peroxynitrite radicals. Since most of the ionizing radiation-induced cellular damage is caused by hydroxyl radicals, we hypothesize that a treatment combining radiotherapy with aerosol inhalation of a hydrogen-rich solution may be an effective and novel prevention strategy for radiation pneumonitis (hydrogen is explosive, while a hydrogen-rich solution such as physiological saline saturated with molecular hydrogen is safer).
Medical science monitor: international medical journal of experimental and clinical research 04/2011; 17(4):HY1-4. · 1.70 Impact Factor
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ABSTRACT: Bone marrow is a major site of radiation injury. The extreme sensitivity of bone marrow cells to genotoxic stress largely determines the adverse side effects of radiation. CpG-oligodeoxynucleotide (ODN) is known to be radioprotective in extramedullary hemopoiesis, but its effect on bone marrow hemopoiesis remains unknown. In this study, we investigated whether CpG-ODN ameliorated hemopoiesis radiation injury when administered after total-body irradiation (TBI). Mice were treated with 50 μg of CpG-ODN via intraperitoneal injection (i.p) 30 min., 24 and 48 hr after TBI. Our results show that CpG-ODN was able to mediate the activation of nuclear factor κB (NF-κB) via degradation of inhibitor NF-κB (IκB-α), and some oxidative stress parameters (malondialdehyde, glutathione and superoxide dismutase) showed significant differences between the radiation control group and the radiation and administration of CpG-ODN group. White blood cell count, bone marrow cell count and bone marrow histological examination indicated that CpG-ODN minimized bone marrow damage induced by radiation. Exogenous colony-forming unit-spleen count indicated that CpG-ODN reduced primitive hemopoietic stem cell damage and reconstituted the hemopoietic system after TBI. The survival of mice was also enhanced after various levels of TBI. The calculated dose reduction factor was 1.2. Thus, we conclude that CpG-ODN may contribute to the amelioration of hemopoiesis radiation injury.
Basic & Clinical Pharmacology & Toxicology 03/2011; 109(1):11-6. · 2.18 Impact Factor
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ABSTRACT: CpG-oligodeoxynucleotide (ODN), a synthetic analog of bacteria DNA, has attracted attention because it activates cells of an adaptive immune system and the innate immune system. In this study, we investigated whether CpG-ODN has radioprotective effects, when administered after total-body irradiation (TBI). Mice were treated with 50 µg CpG-ODN via intraperitoneal injection (i.p) within 30 min, 24 h and 48 h after TBI. Our results showed that the survival rate was enhanced at various levels of TBI. The calculated dose reduction factor (DRF) was 1.2. Bone marrow cell count and bone marrow histological examination indicated that CpG-ODN minimized the bone marrow damage induced by TBI. The data of the white blood cell (WBC) count, exogenous (CFU-S) and endogenous (endoCFU-S) colony forming unit-spleen count demonstrated that CpG-ODN reduced primitive hematopoietic stem cells damage and reconstituted hematopoiesis after TBI. Thus, we suggested that CpG-ODN had the potential to contribute to the improvement of the survival rate and limitation of myelosuppression induced by TBI.
Journal of Radiation Research 01/2011; 52(6):828-33. · 1.68 Impact Factor
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ABSTRACT: Dendritic cells (DCs) are the most potent antigen-presenting cells and play a crucial role in the regulation of immune response and migration of DCs into secondary lymphoid tissues also play an important role in the initiation of innate and adaptive immunity. Radiation therapy is now a routine treatment for certain types of cancer and over 20 percent of cancer patients will require radiation therapy during the treatment of their disease. However, the influence of ionizing irradiation on the migratory ability of DCs is largely unknown. In this article, we report that γ ray irradiation can significantly inhibit LPS-triggered up regulation of CCR7 expression and PGE2 production by DC, thus impairing DC migration towards CCL19 in vitro and in vivo. Moreover, γ ray exposed DC also displayed an increased apoptosis rate and decreased cell viability. Furthermore, we demonstrate that exogenous PGE2 can partly reduce the gamma-ray induced migratory impairment and restored CCR7 expression of DC. Our work suggests that γ irradiation affects DC function at multiple steps during the immune response including DC migration, and that PGE2, via control of CCR7 expression, is an important regulator of DC migration.
International journal of biological sciences 01/2011; 7(2):168-79. · 2.70 Impact Factor
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ABSTRACT: Ionizing radiation (IR) is a well-known carcinogen, however the mechanism of radiation induced thymic lymphoma is not well known. Moreover, an easy and effective method to protect mice from radiation induced thymic lymphoma is still unknown. Hydrogen, or H(2), is seldom regarded as an important agent in medical usage, especially as a therapeutic gas. Here in this study, we found that H(2) protects mice from radiation induced thymic lymphoma in BALB/c mice.
International journal of biological sciences 01/2011; 7(3):297-300. · 2.70 Impact Factor
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Cong Liu,
Bailong Li,
Ying Cheng,
Jing Lin,
Jun Hao,
Shuyu Zhang,
R E J Mitchel,
Ding Sun,
Jin Ni,
Luqian Zhao,
Fu Gao, Jianming Cai
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ABSTRACT: Dysregulation of certain microRNAs (miRNAs) in cancer can promote tumorigenesis, metastasis and invasion. However, the functions and targets of only a few mammalian miRNAs are known. In particular, the miRNAs that participates in radiation induced carcinogenesis and the miRNAs that target the tumor suppressor gene Big-h3 remain undefined. Here in this study, using a radiation induced thymic lymphoma model in BALB/c mice, we found that the tumor suppressor gene Big-h3 is down-regulated and miR-21 is up-regulated in radiation induced thymic lymphoma tissue samples. We also found inverse correlations between Big-h3 protein and miR-21 expression level among different tissue samples. Furthermore, our data indicated that miR-21 could directly target Big-h3 in a 3'UTR dependent manner. Finally, we found that miR-21 could be induced by TGFβ, and miR-21 has both positive and negative effects in regulating TGFβ signaling. We conclude that miR-21 participates in radiation induced carcinogenesis and it regulates TGFβ signaling.
International journal of biological sciences 01/2011; 7(3):347-63. · 2.70 Impact Factor
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Cong Liu,
Chuanfeng Zhou,
Fu Gao,
Shengyun Cai,
Chao Zhang,
Luqian Zhao,
Fang Zhao,
Fei Cao,
Jing Lin,
Yanyong Yang,
Jin Ni,
Jun Jia,
Wei Wu,
Li Zhou,
Jianguo Cui,
Wei Zhang,
Bailong Li, Jianming Cai
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ABSTRACT: MiR-34a, a direct target of p53, has shown to exert potent anti-proliferative effects. It has also been found that miR-34a can be induced by irradiation in vitro and in vivo. However, the relationship between miR-34a and radio-sensitivity, and its potential diagnostic significance in radiation biology, remain unclear. This study found that differing responses to ionizing radiation (IR) of young and adult mice were related to miR-34a. First, we found that miR-34a could be induced in many organs by radiation of both young and adult mice. However, the level of miR-34a induced by young mice was much higher when compared to adult mice. Next, we found that miR-34a played a critical role in radio-sensitivity variations of different tissues by enhancing cell apoptosis and decreasing cell viability. We also found that the induction of miR-34a by radiation was in a p53 dependent manner and that one possible downstream target of miR-34a that lead to different radio-sensitivity was the anti-apoptosis molecular Bcl-2. However, over-expression of miR-34a and knockdown of Bcl-2 could significantly enhance the radio-sensitivity of different cells while inhibition of miR-34a could protect cells from radiation injury. Finally, we concluded that miR-34a could be stable in serum after IR and serve as a novel indicator of radiation injury. Taken together, this data strongly suggests that miR-34a may be a novel indicator, mediator and target of radiation injury, radio-sensitivity and radioprotection.
International journal of biological sciences 01/2011; 7(2):221-33. · 2.70 Impact Factor
