To study the effects of low dose radiation (LDR) on tumor apoptosis, cellcycle progression and changes of apoptosis-related protein Bcl-2 in tumor-bearing mice. Methods:Male mice of Kunming strain were implanted subcu...To study the effects of low dose radiation (LDR) on tumor apoptosis, cellcycle progression and changes of apoptosis-related protein Bcl-2 in tumor-bearing mice. Methods:Male mice of Kunming strain were implanted subcutaneously with S180 sarcoma cells in the left inguenas an in situ experimental animal model. Seven days later, the mice were subjected to 75 mGywhole-body γ-irradiation. At 24 and 48 h after the irradiation, all mice were sacrificed. The tumorsizes were measured, and tumor cell apoptosis and cell cycle progression were analyzed by flowcytometry. The expression of apoptosis-related protein Bcl-2 and the apoptotic rate of tumor cellswere observed by immunohistochemistry and electron microscopy. Results: Tumors grew significantlyslower after LDR (P 【 0.05). The tumor cells were arrested in G1 phrase and the expression of Bcl-2protein decreased at 24 h. Apoptotic rate of tumor cells was increased significantly at 48 h afterLDR (P 【 0.01). Conclusion: LDR could cause a G1-phase arrest and increase the apoptosis of tumorcells through the low level of apoptosis-related protein bcl-2 in the tumor-bearing mice. Theorganized immune function and anti-tumor ability are markedly increased after LDR. Our studyprovides practical evidence of clinical application to cancer treatment.展开更多
Summary: The study examined the role of endoplasmic reticulum stress (ERS) and signaling pathways of inositol-requiring enzyme-1 (IRE1), RNA-activated protein kinase-like ER kinase (PERK) and activating transcr...Summary: The study examined the role of endoplasmic reticulum stress (ERS) and signaling pathways of inositol-requiring enzyme-1 (IRE1), RNA-activated protein kinase-like ER kinase (PERK) and activating transcription factor-6 (ATF6) in apoptosis of mouse testicular cells treated with low-dose radiation (LDR). In the dose-dependent experiment, the mice were treated with whole-body X-ray irradiation at different doses (25, 50, 75, 100 or 200 mGy) and sacrificed 12 h later. In the time-dependent experiment, the mice were exposed to 75 mGy X-ray irradiation and killed at different time points (3, 6, 12, 18 or 24 h). Testicular cells were harvested for experiments. H202 and NO concentrations, and Ca2+-ATPase activity were detected by biochemical assays, the calcium ion concentration ([Ca2+]i) by flow cytometry using fluo-3 probe, and GRP78 mRNA and protein expressions by quantitative real-time RT-PCR (qRT-PCR) and Western blotting, respectively. The mRNA expressions of S-XBP1, JNK, caspase-12 and CHOP were measured by qRT-PCR, and the protein expressions of IREla, S-XBP1, p-PERK, p-elF2a, ATF6 p50, p-JNK, pro-caspase-12, cleaved caspase-12 and CHOP by Western blot- ting. The results showed that the concentrations of H202 and NO, the mR_NA expressions of GRP78, S-XBP1, JNK, caspase-12 and CHOP, and the protein expressions of GRP78, S-XBP1, IREla, p-PERK, p-elF2a, ATF6 p50, p-JNK, pro-caspase-12, cleaved caspase-12 and CHOP were significantly increased in a time- and dose-dependent manner after LDR. But the [Ca2]i and Ca2-ATPase activities were sig nificantly decreased in a time and dose-dependent manner. It was concluded that the ERS, regulated by IRE 1, PERK and ATF6 pathways, is involved in the apoptosis of testicular cells in LDR mice, which is associated with ERS-apoptotic signaling molecules of JNK, caspase-12 and CHOP.展开更多
Objective This paper is to explore the DNA repair mechanism of immune adaptive response (AR) induced by low dose radiation (LDR), the changes of mRNA levels and protein expressions of p53, ATM, DNA-PK catalytic su...Objective This paper is to explore the DNA repair mechanism of immune adaptive response (AR) induced by low dose radiation (LDR), the changes of mRNA levels and protein expressions of p53, ATM, DNA-PK catalytic subunit (DNA-PKcs) and PARP-1 genes in the LDR-induced AR in EL-4 cells. Methods The apoptosis and cell cycle progression of EL-4 cells were detected by flow cytometry in 12 h after the cells received the pre-exposure of 0.075 Gy X-rays (inductive dose, D 1) and the succeeding high dose irradiation (challenge dose, D2; 1.0, 1.5, and 2.0 Gy X-rays, respectively) with or without wortmannin (inhibitor of ATM and DNA-PK) and 3-aminobenzamid (inhibitor of PARP-1). And the protein expressions and mRNA levels related to these genes were detected with flow cytometry and reverse transcription-polymerase chain reaction in 12 h after irradiation with D2. Results The mRNA and protein expressions of p53 and PARP-1 in EL-4 cells in the D1 + D2 groups were much lower than those in the D2 groups, and those of PARP-1 in the 3-AB + D2 and the 3-AB + D1 + D2 groups were much lower than those in the D2 and the D1 + D2 groups. The percentage of apoptotic EL-4 cells in the 3-AB + D1 + D2 groups was much higher than that in the D1 + D2 groups, that in the G0/G1 and the G2 + M phases was much higher, and that in the S phase were much lower. Although the ATM and DNA-PKcs mRNA and protein expressions in wortmannin + D1 + D2 groups were much lower than those in the D1 + D2 groups, there were no significant changes in the apoptosis and cell cycle progression between the wortmannin + D1 + D2 and the D1 + D2 groups. Conclusion PARP-1 and p53 might play important roles in AR induced by LDR.展开更多
Objective To investigate whether apoptosis induced by low-dose radiation (LDR) is regulated by mitochondrial pathways in testicular cells. Methods Male mice were exposed to whole-body LDR, and changes in mitochondri...Objective To investigate whether apoptosis induced by low-dose radiation (LDR) is regulated by mitochondrial pathways in testicular cells. Methods Male mice were exposed to whole-body LDR, and changes in mitochondrial function and in expression of apoptotic factors were analyzed in the testicular cells as follows. Total nitric-oxide synthase (T-NOS) and Na+/K+ ATPase activities were biochemically assayed. Reactive oxygen species (ROS) and mitochondrial membrane potential (Adjm) were determined by flow cytometry using fluorescent probes. Levels of mRNAs encoding cytochrome c (Cyt c) and apoptosis-inducing factor (AIF) were quantified by real-time reverse-transcription PCR (RT-PCR). Expression of Cyt c, AIF, caspase-9, and caspase-3 at the protein level was assessed by western blotting and immunohistochemistry. Results LDR induced an increase in T-NOS activity and ROS levels, and a decrease in Na+/K~ ATPase activity and mitochondrial A^m, in the testicular cells. The intensity of these effects increased with time after irradiation and with dose. The cells showed remarkable swelling and vacuolization of mitochondria, and displayed a time- and dose-dependent increase in the expression of Cyt c, AIF, procaspase-9, and procaspase-3. Activation of the two procaspases was confirmed by detection of the cleaved caspases. The changes in expression of the four apoptotic factors were mostly limited to spermatogonia and spermatocytes. Conclusion LDR can induce testicular cell apoptosis through mitochondrial signaling pathways展开更多
The mechanisms occurring when the switched temperature technique is applied,as an accelerated enhanced low dose rate sensitivity(ELDRS)test technique,are investigated in terms of a specially designed gate-controlled l...The mechanisms occurring when the switched temperature technique is applied,as an accelerated enhanced low dose rate sensitivity(ELDRS)test technique,are investigated in terms of a specially designed gate-controlled lateral PNP transistor(GLPNP)that used to extract the interface traps(Nit)and oxide trapped charges(Not).Electrical characteristics in GLPNP transistors induced by ^(60)Co gamma irradiation are measured in situ as a function of total dose,showing that generation of Nit in the oxide is the primary cause of base current variations for the GLPNP.Based on the analysis of the variations of Nit and Not,with switching the temperature,the properties of accelerated protons release and suppressed protons loss play critical roles in determining the increased Nit formation leading to the base current degradation with dose accumulation.Simultaneously the hydrogen cracking mechanisms responsible for additional protons release are related to the neutralization of Not extending enhanced Nit buildup.In this study the switched temperature irradiation has been employed to conservatively estimate the ELDRS of GLPNP,which provides us with a new insight into the test technique for ELDRS.展开更多
Objective To investigate the inhibition of low dose radiation (LDR) on S180 sarcomas and its modulation of MMP-2 and TIMP-2 in mice. Methods $180 subcutaneously implanted tumor model mice were randomly divided into ...Objective To investigate the inhibition of low dose radiation (LDR) on S180 sarcomas and its modulation of MMP-2 and TIMP-2 in mice. Methods $180 subcutaneously implanted tumor model mice were randomly divided into two groups: control (N) and low dose radiation (LDR) groups. N mice were sacrificed after 12 h, whereas LDR mice were sacrificed after 12 (LDR-12 h), 24 (LDR-24 h), 48 (LDR-48 h), and 72 (LDR-72 h) h. Thereafter, we measured the tumor volumes. Histopathology was performed, and P-V immunohistochemistry was applied to assess MMP-2 and TIMP-2 expression. Results Compared with the control group, the tumor growth was significantly inhibited in the LDR groups (P 〈 0.05). MMP-2 expression was considerably reduced in LDR-24h (P 〈 0.05) and LDR-48h (P 〈 0.05), whereas the change of TIMP-2 was not obvious in the LDR groups (P 〉 0.05) in contrast to that of the control group. Conclusion LDR can effectively suppress the growth of S180 implanted tumors by reducing MMP-2, which is associated with invasion and metastasis.展开更多
Objective To investigate whether low-dose fractionated radiation(LDFRT) could enhance cisplatin sensitivity in drug-resistant human ovarian cancer cells SKOV3/DDP, and to further explore the underlying mechanism.Metho...Objective To investigate whether low-dose fractionated radiation(LDFRT) could enhance cisplatin sensitivity in drug-resistant human ovarian cancer cells SKOV3/DDP, and to further explore the underlying mechanism.Methods SKOV3/DDP ovarian cancer cells were divided into three groups as follows: control, LDFRT, and conventional-dose radiation groups. Cells from all three groups were treated with different concentrations of cisplatin(0, 1.25, 2.5, 5, 10, and 20 μg/m L) for 48 h. The proliferation inhibition rate was investigated using the cell counting kit 8(CCK8). The rate of apoptosis was determined by flow cytometry(FCM). Protein levels of AKT, P-AKT, GSK-3β, P-GSK-3β, P21, cyclin D1, and P27 were examined by Western blotting. Results As expected, LDFRT significantly reduced the half-maximal inhibitory concentration(IC50) of cisplatin and promoted apoptosis in SKOV3/DDP cells. Moreover, in the LDFRT group, protein levels of P-AKT, P-GSK-3β, and cyclin D1 were markedly decreased, those of P21 and P27 were greatly increased, and total AKT and GSK-3β levels showed no significant difference compared to those in both the control and conventional-dose radiation groups.Conclusion LDFRT sensitizes resistant SKOV3/DDP ovarian cancer cells to cisplatin through inactivation of PI3 K/AKT/GSK-3β signaling.展开更多
A clear relationship between dose of radiation and mortality in humans is still not known because of lack of human data that would enable to determine human tolerance in total body irradiation. Human data for analysis...A clear relationship between dose of radiation and mortality in humans is still not known because of lack of human data that would enable to determine human tolerance in total body irradiation. Human data for analysis have been primarily from radiation accidents, radiotherapy and the atomic bomb victims. A general formula that predicts mortality probability as a function of dose rate and duration of exposure to acute high dose ionizing radiation in humans was published by the author, applying the “probacent” model to the reported data on animal-model-predicted dose versus mortality. In this study, the “probacent” model is applied to the data on dose versus cancer mortality risk, published by the United Nations (UNSCEAR, 2010) and other investigators to construct general formulas expressing a relationship between dose and solid cancer or leukemia mortality probability after exposure to acute low dose ionizing radiation in humans. There is a remarkable agreement between formula-derived and published values of dose and solid cancer or leukemia mortality probability (p > 0.99). The general formula might be helpful in preventing radiation hazard and injury in acute low dose ionizing radiation, and for safety in radiotherapy.展开更多
Objective: By studying the influence of low-dose total body irradiation to proliferating cell nuclear antigens (PCNA), epidermal growth factor receptor (EGFR), erythropoietin (EPO) and vascular endothelial grow...Objective: By studying the influence of low-dose total body irradiation to proliferating cell nuclear antigens (PCNA), epidermal growth factor receptor (EGFR), erythropoietin (EPO) and vascular endothelial growth factor receptor (VEGFR) of tumor tissues in mice bearing S180 sarcoma, to further explore the mechanism of low doses radiation. Methods:S180 sarcoma cells were implanted subcutaneously into 58 male Kunming mice. Randomly these mice were divided into sham-irradiation (S) group and low-dose radiation (LDR) group. 12 days after implantation, the mice in LDR group were once delivered 75 mGy total-body ^60Co y-ray irradiation, while the mice in S group were left without irradiation. Then the mice in LDR group were executed at 6 h (LDR-6h group), 12 h (LDR-12 h group), 24 h (LDR-24 h group), 48 h (LDR-48 h group) and 72 h (LDR-72h group) after irradiation. Tumor tissues were weighed and histological observed. Immunohistochemical staining was used to detect the expression of PCNA, VEGF, EPO and VEGFR of tumor tissues. Results: Though there was no significant difference between LDR group and S group in tumor weight, after irradiation the expression of PCNA and EPO of tumor tissues in LDR group decreased with time. LDR-24h, LDR-48h and LDR-72h groups were all statistically significantly different from S group. The expression of EGFR and VEGFR also decreased, and LDR-24h group was the lowest (P 〈 0.05). Conclusion: Seventy-two h after low-dose total body irradiation, there was no significant change in tumor size of mice bearing S180 sarcoma. Low-dose total body radiation decreased the expression of PCNA inhibiting tumor growth; reduced the expression of EGFR in tumor tissue impacting the signal transduction of tumor cells. The study also indicated that low-dose total body irradiation, within a certain period of time, can decrease the expression of hypoxia factor EPO and VEGFR, which may improve the situation of tumor hypoxia and radiosensitivity of tumor itself.展开更多
BACKGROUND: Bone marrow-derived mesenchymal stem cells (BMSCs) are a potentially useful source for cell replacement therapy following spinal cord injury. However, the homing characteristics of BMSCs in vivo remain ...BACKGROUND: Bone marrow-derived mesenchymal stem cells (BMSCs) are a potentially useful source for cell replacement therapy following spinal cord injury. However, the homing characteristics of BMSCs in vivo remain unclear. Low-dose radiation has been shown to promote homing of BMSCs to exposed sites. OBJECTIVE: To investigate the effects of low-dose local radiation to non-injured areas on the ability of human BMSCs to home to the injured mouse spinal cord, as well as recovery of spinal cord injury. DESIGN, TIME AND SE'I-FING: A randomized, controlled, animal experiment was performed at the Central Laboratory, Second Affiliated Hospital of Soochow University between October 2007 and October 2008. MATERIALS: BMSCs were isolated from four adult, human donors. METHODS: Fifty adult, female, Balb/c mice were subjected to adjusted weight-drop impact resulting in complete paraplegia. Three days later, mice were randomly assigned to a radiation + transplantation group (n = 23) and a transplantation group (n = 20). In total, 2 x 106 carboxyfluorescein diacetate succinimidyl ester-labeled BMSCs were injected into each mouse via the caudal vein. Mice in the radiation + transplantation group received 2.5 Gy local X-ray irradiation 2 hours before BMSCs injection. MAIN OUTCOME MEASURES: The homing of BMSCs to injured cord and irradiated skin after transplantation was observed by fluorescence microscope; the structure recovery of injured cord was assessed by magnetic resonance imaging. RESULTS: Compared with the transplantation group, at 24 hours after transplantation, the number of BMSCs was significantly increased in the injured area and the exposed site (P 〈 0.05), and inflammation and edema were significantly alleviated in the injured cord in the radiation + transplantation group. CONCLUSION: Local low-dose radiation has the potential to promote homing of BMSCs and recovery of spinal cord injury, although the radiated region was not injured area.展开更多
The influence of low tube voltage in dual source CT(DSCT) coronary artery imaging on image quality and radiation dose and its application value in clinical practice were investigated. Totally, 300 cases of chest pai...The influence of low tube voltage in dual source CT(DSCT) coronary artery imaging on image quality and radiation dose and its application value in clinical practice were investigated. Totally, 300 cases of chest pain with low body mass index(BMI 〈18.5 kg/m2) subjected to DSCT coronary artery imaging were prospectively enrolled. The heart rate in all patients were greater than 65/min. The retrospective ECG gated scanning mode and simple random sampling method were used to assign the patients into groups A, B and C(n=100 each). The patients in groups A, B and C experienced 120-, 100-, and 80-kV tube voltage imaging respectively, and the image quality was evaluated. The CT volume dose index(CTDIvol) and dose length product(DLP) were recorded, and the effective dose(ED) was calculated in each group. The image quality scores and radiation doses in groups were compared, and the influence of tube voltage on image quality and radiation dose was analyzed. The results showed that the excellent rate of image quality in groups A, B and C was 95.69%, 94.72% and 96.33% respectively with the difference being not statistically significant among the three groups(P〉0.05). The CTDIvol values in groups A, B and C were 51.35±12.21, 21.28±7.13 and 6.34±3.34 mGy, respectively, with the difference being statistically significant(P〈0.05). The ED values in groups A, B and C were 9.27±1.63, 4.56±2.29 and 2.29±1.69 mSv, respectively, with the difference being statistically significant(P〈0.05). It was suggested that for the patients with low BMI, the application of DSCT coronary artery imaging with low tube voltage can obtain satisfactory image quality, and simultaneously, significantly reduce the radiation dose.展开更多
AIM:To evaluate the feasibility of low contrast medium and radiation dose for hepatic computed tomography(CT) perfusion of rabbit VX2 tumor.METHODS:Eleven rabbits with hepatic VX2 tumor underwent perfusion CT scanning...AIM:To evaluate the feasibility of low contrast medium and radiation dose for hepatic computed tomography(CT) perfusion of rabbit VX2 tumor.METHODS:Eleven rabbits with hepatic VX2 tumor underwent perfusion CT scanning with a 24-h interval between a conventional tube potential(120 k Vp) protocol with 350 mg I/m L contrast medium and filtered back projection,and a low tube potential(80 k Vp) protocol with 270 mg I/m L contrast medium with iterative reconstruction.Correlation and agreement among perfusion parameters acquired by the conventional and low dose protocols were assessed for the viable tumor component as well as whole tumor.Image noise and tumor-to-liver contrast to noise ratio during arterial and portal venous phases were evaluated.RESULTS:A 38% reduction in contrast medium dose(360.1 ± 13.3 mg I/kg vs 583.5 ± 21.5 mg I/kg,P < 0.001) and a 73% decrease in radiation dose(1898.5 m Gy·cm vs 6951.8 m Gy·cm) were observed.Interestingly,there was a strong positive correlation in hepatic arterial perfusion(r = 0.907,P < 0.001;r = 0.879,P < 0.001),hepatic portal perfusion(r = 0.819,P = 0.002;r = 0.831,P = 0.002),and hepatic blood flow(r = 0.945,P < 0.001;r = 0.930,P < 0.001) as well as a moderate correlation in hepatic perfusion index(r = 0.736,P = 0.01;r = 0.636,P = 0.035) between the low dose protocol with iterative reconstruction and the conventional protocol for the viable tumor component and the whole tumor.These two imaging protocols provided a moderate but acceptable agreement for perfusion parameters and similar tumorto-liver CNR during arterial and portal venous phases(5.63 ± 2.38 vs 6.16 ± 2.60,P = 0.814;4.60 ± 1.27 vs 5.11 ± 1.74,P = 0.587).CONCLUSION:Compared with the conventional protocol,low contrast medium and radiation dose with iterative reconstruction has no significant influence on hepatic perfusion parameters for rabbits VX2 tumor.展开更多
WT5”BZ] To study the molecular mechanism of the stimulatory effect of low dose radiation(LDR) on T cell activation. [WT5”BX]Methods.[WT5”BZ] Thymocytes from Kunming mice exposed to whole body irradiation(WBI) with ...WT5”BZ] To study the molecular mechanism of the stimulatory effect of low dose radiation(LDR) on T cell activation. [WT5”BX]Methods.[WT5”BZ] Thymocytes from Kunming mice exposed to whole body irradiation(WBI) with different doses of X rays were analyzed for the changes in signal molecules of the phospholipase C phosphatidylinositol biphosphate(PLC IP2) and G protein adenylate cyclase(AC) pathways. [WT5”BX]Results.[WT5”BZ]It was found that[Ca 2+ ] i increased in response to doses within 0 2 Gy which was most marked after 0 075 Gy and the increase was accentuated in the presence of Con A. The changes in CD3 and calcineurin(CN) expression of the thymocytes followed the same pattern as the alterations in [Ca 2+ ] i after LDR. The expression of α,β1 and β2 isoforms of protein kinase C(PKC) was all up regulated after 0 075 Gy with the increase in PKC β1 expression being most marked. The cAMP/cGMP ratio and PKA activity of the thymocytes was lowered after low dose radiation and increased after doses above 0 5 Gy in a dose dependent manner, thus giving rise to J shaped dose response curves. The Ca antagonist TMB 8 and cAMP stimulant cholera toxin suppressed the augmented thymocyte proliferation induced by LDR. [WT5”BX]Conclusion.[WT5”BZ]Data presented in the present paper suggest that activation of the PLC PIP2 signal pathway and suppression of the AC cAMP signal pathway are involved in the stimulation of the thymocytes following WBI with low dose X rays.展开更多
Human lymphocytes pre-exposed to 10 mGy or 50 mGy of X-rays become less sensitive to subsequent large dose irradiation, exhibited lower rate of chromosome aberration than expected. This adaptive response could be inhi...Human lymphocytes pre-exposed to 10 mGy or 50 mGy of X-rays become less sensitive to subsequent large dose irradiation, exhibited lower rate of chromosome aberration than expected. This adaptive response could be inhibited by cycloheximide, a protein synthesis inhibitor for successive 2 h period ranging from 0.5h before to 4h after the low dose exposure, indicating that the adaptive response was directly related with the protein synthesis.展开更多
It is first reported in the present paper that whole-body irradiation (WBI) with low dose X-rays could increase intracellular calcium ions ([Ca2+]i) and stimulate protein kinase C (PKC) activity of mouse lymphocytes. ...It is first reported in the present paper that whole-body irradiation (WBI) with low dose X-rays could increase intracellular calcium ions ([Ca2+]i) and stimulate protein kinase C (PKC) activity of mouse lymphocytes. Following WBI of male Kunming micc With 75 mGy X-rays at a dose rate of 12.5 mGy/min the mobilization of [Ca2+]i with Con A in CD4+ and CD8+ Cells in the thymus and spleen was potentiated and the amplitude of [Ca2+], mobilization in thymocytes in response to anti-CD3 monoclonal antibody increased with time from 4 to 24 h following low dose radiation. The PKC activity in the homogenate of spleen was markedly stimulated 12 h after WBl with 75 mGy, reaching its peak value at 24-48 h and coming down to lower than normal on day 7. However, the PKC activity in the separated T lymphocytes reached its peak value at 12 h and that in the B lymphocytes reached its peak value on day 4, both coming down to below control on day 7. The implications of this facilitation of signal transduction in T lymphocytes in the mechanism of immunoenhancement after low dose radiation were discussed展开更多
Objective To investigate the mechanism of low-dose fractionated radiation on reversing cisplatin resistance in ovarian carcinoma via vascular endothelial growth factor(VEGF) and mammalian target of rapamycin(mTOR) in ...Objective To investigate the mechanism of low-dose fractionated radiation on reversing cisplatin resistance in ovarian carcinoma via vascular endothelial growth factor(VEGF) and mammalian target of rapamycin(mTOR) in vivo.Methods Human cisplatin-resistant ovarian carcinoma cells(SKOV3/DDP) were injected into nude mice to establish ovarian cancer xenografts. The mice were randomly divided into three groups: a control group, a low-dose fractionated radiation(LDRFT) group, and a conventional-dose radiation group. Each group was exposed to 0 cGy, 50 cGy, and 200 cGy radiation, respectively, for 4 weeks, up to a total of 8.0 Gy. Mice in the LDFRT group were irradiated twice daily with 6 hour intermissions on day 1 and 2 of every week for a total of 4 weeks. Conventional-dose group mice were given a single 200 cGy radiation dose on the first day each week for a total of 4 weeks. Maximum horizontal and vertical diameters of the tumors were measured every other day and used to create a tumor growth curve. After 4 weeks of irradiation, we dissected the tumor tissue and calculated the tumor inhibition rate. RT-PCR detected the expression of VEGF and m TOR, and Western blots detected the expression of corresponding proteins.Results Both LDRFT and conventional-dose radiation inhibited the growth of tumor cells, and growth of tumors in the two radiation groups compared with growth in the control group were significantly different(P < 0.05). The rate of tumor inhibition in the LDFRT group(37.5603%) was lower than in the conventionaldose group(47.4446%), but there was no significant difference(P 0.05). Compared with the other two groups, the m RNA expression of VEGF was significantly lower in the LDFRT group(P < 0.05), but there was no obvious difference between the conventional-dose and control groups. There was no obvious difference in the m RNA expression of m TOR among the three groups, but the expression of the protein p-m TOR was lower in the LDFRT group(P < 0.05), as confirmed by Western blotting.Conclusion LDFRT is as effective at inhibiting the growth of tumor cells as conventional-dose radiation. In addition, LDFRT could deregulate the expression of VEGF and p-m TOR, and may therefore play a vital role in reversing cisplatin resistance in ovarian cancer.展开更多
This work was supported by the National Natural Science Foundation of China (No. 3870902). Objective: To determine the NK activity of lymphocyte subsets and the effects of low dose radiation. Methods: Lymphocyte s...This work was supported by the National Natural Science Foundation of China (No. 3870902). Objective: To determine the NK activity of lymphocyte subsets and the effects of low dose radiation. Methods: Lymphocyte subsets were separated by monoclonal antibodies. The NK activity of each subset on tumor cells was detected by radioactive release method. Results: The results showed that besides NK cells, CD 4, CD 8 and B cells alone can kill tumor cells. But the cellkilling activity of NK cells appeared to be strongest. There was synergistic effect between CD 4 and NK cells. The activity of mixed lymphocytes was more than that of only one subset. The effect of low dose radiation (LDR) on NK activity of panlymphocytes or NK cells was different. Conclusion: This paper demonstrated that NK activity of mononuclear cells was called “NK activity of lymphocytes”, but it is not true. Only when NK cells were separated by monoclonal antibodies, its killer activity can be called “activity of NK cells”.展开更多
It is represented the review about the effect of low doses of ionized radiation on different types of biological objects (Japanese quail embryos, Aspergillus niger, Spirostomum ambiguum Ehrbg., mezenchim stem cells of...It is represented the review about the effect of low doses of ionized radiation on different types of biological objects (Japanese quail embryos, Aspergillus niger, Spirostomum ambiguum Ehrbg., mezenchim stem cells of mice bone brain, dry seeds of the highest plants, blood lymphocytes of pilots and cosmonauts) and water medium. In model experiments under the chronic ionized radiation in doses comparable with the doses of ionized radiation inside the orbital space stations and during the flight in interplanetary space was shown alike with morphological deviations (Japanese quail embryos, Aspergillus niger), the phenomenon of radiation hormezis (Aspergillus niger, mezenchim stem cells), the increasing of the germination of seeds, the decreasing of spontaneous motion activity of spirostoms and DNA damage, chromosome aberrations and the increased radio-sensitivity to adding radiation load in blood lymphocytes. These data testified the fact that the definite factor of ionized radiation effect is the changing of water medium state. Thus under the interplanetary cosmic flight and long stay on the orbit in the region of magnetosphere the studying kinds of radiation first effected on the water medium of organism as a result morpho-functional structures were changed.展开更多
Objective: The aim of this study was to explore the effect of low dose radiation on cytokine excreted by mice inbreathing of atomization of PYM. Methods: Kunming male mice were randomly divided into three groups: b...Objective: The aim of this study was to explore the effect of low dose radiation on cytokine excreted by mice inbreathing of atomization of PYM. Methods: Kunming male mice were randomly divided into three groups: blank group, PYM group (P group), low dose radiation + PYM group (P + L group). Mice of P + L group were given whole body low dose radiation 75 mGY, dose rate were 12.5 mGY/min. After 6 h, mice in both P + L group and P group were given inbreathe of atomization of PYM, concentration was 2 mg/mL. Mice were sacrificed after the dl, d7, d14, d21 and d28, IL-6 were detected in alveolar irrigating solution. The tissue samples of mice lung were fixed in 10% formalin, TNF-α and TGF-β were analyzed by immuno- histochemistry. Results: Compared with P group, IL-6 in low dose radiation + PYM group were lower, near to blank group, the difference had notable statistical significance on the dl and the d7, while on the d14, d21, d28, the difference had not statisti- cal significance. It suggested that low dose radiation could reduce the resection of IL-6 at the begin of lung injure induced by low dose radiation. The expression of TGF-β and TNF-α in P + L group were lower than that in P group, but the difference in the two groups had statistical significance by gray analysis P 〈 0.05. Conclusion: In the early stage of lung injure caused by PYM in mice, low dose radiation of 75 mGY can reduce the secretion of IL-6, decrease the production of TGF-β and TNF-α.展开更多
文摘To study the effects of low dose radiation (LDR) on tumor apoptosis, cellcycle progression and changes of apoptosis-related protein Bcl-2 in tumor-bearing mice. Methods:Male mice of Kunming strain were implanted subcutaneously with S180 sarcoma cells in the left inguenas an in situ experimental animal model. Seven days later, the mice were subjected to 75 mGywhole-body γ-irradiation. At 24 and 48 h after the irradiation, all mice were sacrificed. The tumorsizes were measured, and tumor cell apoptosis and cell cycle progression were analyzed by flowcytometry. The expression of apoptosis-related protein Bcl-2 and the apoptotic rate of tumor cellswere observed by immunohistochemistry and electron microscopy. Results: Tumors grew significantlyslower after LDR (P 【 0.05). The tumor cells were arrested in G1 phrase and the expression of Bcl-2protein decreased at 24 h. Apoptotic rate of tumor cells was increased significantly at 48 h afterLDR (P 【 0.01). Conclusion: LDR could cause a G1-phase arrest and increase the apoptosis of tumorcells through the low level of apoptosis-related protein bcl-2 in the tumor-bearing mice. Theorganized immune function and anti-tumor ability are markedly increased after LDR. Our studyprovides practical evidence of clinical application to cancer treatment.
基金supported by the grants from the National Natural Science Foundation of China(No.30970681)Basic Research and Operating Expenses of Jilin University(No.200903116)
文摘Summary: The study examined the role of endoplasmic reticulum stress (ERS) and signaling pathways of inositol-requiring enzyme-1 (IRE1), RNA-activated protein kinase-like ER kinase (PERK) and activating transcription factor-6 (ATF6) in apoptosis of mouse testicular cells treated with low-dose radiation (LDR). In the dose-dependent experiment, the mice were treated with whole-body X-ray irradiation at different doses (25, 50, 75, 100 or 200 mGy) and sacrificed 12 h later. In the time-dependent experiment, the mice were exposed to 75 mGy X-ray irradiation and killed at different time points (3, 6, 12, 18 or 24 h). Testicular cells were harvested for experiments. H202 and NO concentrations, and Ca2+-ATPase activity were detected by biochemical assays, the calcium ion concentration ([Ca2+]i) by flow cytometry using fluo-3 probe, and GRP78 mRNA and protein expressions by quantitative real-time RT-PCR (qRT-PCR) and Western blotting, respectively. The mRNA expressions of S-XBP1, JNK, caspase-12 and CHOP were measured by qRT-PCR, and the protein expressions of IREla, S-XBP1, p-PERK, p-elF2a, ATF6 p50, p-JNK, pro-caspase-12, cleaved caspase-12 and CHOP by Western blot- ting. The results showed that the concentrations of H202 and NO, the mR_NA expressions of GRP78, S-XBP1, JNK, caspase-12 and CHOP, and the protein expressions of GRP78, S-XBP1, IREla, p-PERK, p-elF2a, ATF6 p50, p-JNK, pro-caspase-12, cleaved caspase-12 and CHOP were significantly increased in a time- and dose-dependent manner after LDR. But the [Ca2]i and Ca2-ATPase activities were sig nificantly decreased in a time and dose-dependent manner. It was concluded that the ERS, regulated by IRE 1, PERK and ATF6 pathways, is involved in the apoptosis of testicular cells in LDR mice, which is associated with ERS-apoptotic signaling molecules of JNK, caspase-12 and CHOP.
基金supported by the National Natural Science Foundation of China(30570546 and 30870747)the Natural Science Foundation of Jilin Province (20090458 and 201015183)+1 种基金the Young Teachers Innovative Foundation of Jilin University(421010043430)the Young Scholars Research Foundation Program of China-Japan Union Hospital(2009)
文摘Objective This paper is to explore the DNA repair mechanism of immune adaptive response (AR) induced by low dose radiation (LDR), the changes of mRNA levels and protein expressions of p53, ATM, DNA-PK catalytic subunit (DNA-PKcs) and PARP-1 genes in the LDR-induced AR in EL-4 cells. Methods The apoptosis and cell cycle progression of EL-4 cells were detected by flow cytometry in 12 h after the cells received the pre-exposure of 0.075 Gy X-rays (inductive dose, D 1) and the succeeding high dose irradiation (challenge dose, D2; 1.0, 1.5, and 2.0 Gy X-rays, respectively) with or without wortmannin (inhibitor of ATM and DNA-PK) and 3-aminobenzamid (inhibitor of PARP-1). And the protein expressions and mRNA levels related to these genes were detected with flow cytometry and reverse transcription-polymerase chain reaction in 12 h after irradiation with D2. Results The mRNA and protein expressions of p53 and PARP-1 in EL-4 cells in the D1 + D2 groups were much lower than those in the D2 groups, and those of PARP-1 in the 3-AB + D2 and the 3-AB + D1 + D2 groups were much lower than those in the D2 and the D1 + D2 groups. The percentage of apoptotic EL-4 cells in the 3-AB + D1 + D2 groups was much higher than that in the D1 + D2 groups, that in the G0/G1 and the G2 + M phases was much higher, and that in the S phase were much lower. Although the ATM and DNA-PKcs mRNA and protein expressions in wortmannin + D1 + D2 groups were much lower than those in the D1 + D2 groups, there were no significant changes in the apoptosis and cell cycle progression between the wortmannin + D1 + D2 and the D1 + D2 groups. Conclusion PARP-1 and p53 might play important roles in AR induced by LDR.
基金supported by the National Natural Science Foundation of China (30970681)Basic Research and Operating Expenses of Jilin University (200903116)
文摘Objective To investigate whether apoptosis induced by low-dose radiation (LDR) is regulated by mitochondrial pathways in testicular cells. Methods Male mice were exposed to whole-body LDR, and changes in mitochondrial function and in expression of apoptotic factors were analyzed in the testicular cells as follows. Total nitric-oxide synthase (T-NOS) and Na+/K+ ATPase activities were biochemically assayed. Reactive oxygen species (ROS) and mitochondrial membrane potential (Adjm) were determined by flow cytometry using fluorescent probes. Levels of mRNAs encoding cytochrome c (Cyt c) and apoptosis-inducing factor (AIF) were quantified by real-time reverse-transcription PCR (RT-PCR). Expression of Cyt c, AIF, caspase-9, and caspase-3 at the protein level was assessed by western blotting and immunohistochemistry. Results LDR induced an increase in T-NOS activity and ROS levels, and a decrease in Na+/K~ ATPase activity and mitochondrial A^m, in the testicular cells. The intensity of these effects increased with time after irradiation and with dose. The cells showed remarkable swelling and vacuolization of mitochondria, and displayed a time- and dose-dependent increase in the expression of Cyt c, AIF, procaspase-9, and procaspase-3. Activation of the two procaspases was confirmed by detection of the cleaved caspases. The changes in expression of the four apoptotic factors were mostly limited to spermatogonia and spermatocytes. Conclusion LDR can induce testicular cell apoptosis through mitochondrial signaling pathways
基金Project supported by the National Natural Science Foundation of China(Grant Nos.U1532261 and 1630141)
文摘The mechanisms occurring when the switched temperature technique is applied,as an accelerated enhanced low dose rate sensitivity(ELDRS)test technique,are investigated in terms of a specially designed gate-controlled lateral PNP transistor(GLPNP)that used to extract the interface traps(Nit)and oxide trapped charges(Not).Electrical characteristics in GLPNP transistors induced by ^(60)Co gamma irradiation are measured in situ as a function of total dose,showing that generation of Nit in the oxide is the primary cause of base current variations for the GLPNP.Based on the analysis of the variations of Nit and Not,with switching the temperature,the properties of accelerated protons release and suppressed protons loss play critical roles in determining the increased Nit formation leading to the base current degradation with dose accumulation.Simultaneously the hydrogen cracking mechanisms responsible for additional protons release are related to the neutralization of Not extending enhanced Nit buildup.In this study the switched temperature irradiation has been employed to conservatively estimate the ELDRS of GLPNP,which provides us with a new insight into the test technique for ELDRS.
文摘Objective To investigate the inhibition of low dose radiation (LDR) on S180 sarcomas and its modulation of MMP-2 and TIMP-2 in mice. Methods $180 subcutaneously implanted tumor model mice were randomly divided into two groups: control (N) and low dose radiation (LDR) groups. N mice were sacrificed after 12 h, whereas LDR mice were sacrificed after 12 (LDR-12 h), 24 (LDR-24 h), 48 (LDR-48 h), and 72 (LDR-72 h) h. Thereafter, we measured the tumor volumes. Histopathology was performed, and P-V immunohistochemistry was applied to assess MMP-2 and TIMP-2 expression. Results Compared with the control group, the tumor growth was significantly inhibited in the LDR groups (P 〈 0.05). MMP-2 expression was considerably reduced in LDR-24h (P 〈 0.05) and LDR-48h (P 〈 0.05), whereas the change of TIMP-2 was not obvious in the LDR groups (P 〉 0.05) in contrast to that of the control group. Conclusion LDR can effectively suppress the growth of S180 implanted tumors by reducing MMP-2, which is associated with invasion and metastasis.
文摘Objective To investigate whether low-dose fractionated radiation(LDFRT) could enhance cisplatin sensitivity in drug-resistant human ovarian cancer cells SKOV3/DDP, and to further explore the underlying mechanism.Methods SKOV3/DDP ovarian cancer cells were divided into three groups as follows: control, LDFRT, and conventional-dose radiation groups. Cells from all three groups were treated with different concentrations of cisplatin(0, 1.25, 2.5, 5, 10, and 20 μg/m L) for 48 h. The proliferation inhibition rate was investigated using the cell counting kit 8(CCK8). The rate of apoptosis was determined by flow cytometry(FCM). Protein levels of AKT, P-AKT, GSK-3β, P-GSK-3β, P21, cyclin D1, and P27 were examined by Western blotting. Results As expected, LDFRT significantly reduced the half-maximal inhibitory concentration(IC50) of cisplatin and promoted apoptosis in SKOV3/DDP cells. Moreover, in the LDFRT group, protein levels of P-AKT, P-GSK-3β, and cyclin D1 were markedly decreased, those of P21 and P27 were greatly increased, and total AKT and GSK-3β levels showed no significant difference compared to those in both the control and conventional-dose radiation groups.Conclusion LDFRT sensitizes resistant SKOV3/DDP ovarian cancer cells to cisplatin through inactivation of PI3 K/AKT/GSK-3β signaling.
文摘A clear relationship between dose of radiation and mortality in humans is still not known because of lack of human data that would enable to determine human tolerance in total body irradiation. Human data for analysis have been primarily from radiation accidents, radiotherapy and the atomic bomb victims. A general formula that predicts mortality probability as a function of dose rate and duration of exposure to acute high dose ionizing radiation in humans was published by the author, applying the “probacent” model to the reported data on animal-model-predicted dose versus mortality. In this study, the “probacent” model is applied to the data on dose versus cancer mortality risk, published by the United Nations (UNSCEAR, 2010) and other investigators to construct general formulas expressing a relationship between dose and solid cancer or leukemia mortality probability after exposure to acute low dose ionizing radiation in humans. There is a remarkable agreement between formula-derived and published values of dose and solid cancer or leukemia mortality probability (p > 0.99). The general formula might be helpful in preventing radiation hazard and injury in acute low dose ionizing radiation, and for safety in radiotherapy.
基金Supported by a grant from the National Natural Scientific Foundation of China (No: 30030781)
文摘Objective: By studying the influence of low-dose total body irradiation to proliferating cell nuclear antigens (PCNA), epidermal growth factor receptor (EGFR), erythropoietin (EPO) and vascular endothelial growth factor receptor (VEGFR) of tumor tissues in mice bearing S180 sarcoma, to further explore the mechanism of low doses radiation. Methods:S180 sarcoma cells were implanted subcutaneously into 58 male Kunming mice. Randomly these mice were divided into sham-irradiation (S) group and low-dose radiation (LDR) group. 12 days after implantation, the mice in LDR group were once delivered 75 mGy total-body ^60Co y-ray irradiation, while the mice in S group were left without irradiation. Then the mice in LDR group were executed at 6 h (LDR-6h group), 12 h (LDR-12 h group), 24 h (LDR-24 h group), 48 h (LDR-48 h group) and 72 h (LDR-72h group) after irradiation. Tumor tissues were weighed and histological observed. Immunohistochemical staining was used to detect the expression of PCNA, VEGF, EPO and VEGFR of tumor tissues. Results: Though there was no significant difference between LDR group and S group in tumor weight, after irradiation the expression of PCNA and EPO of tumor tissues in LDR group decreased with time. LDR-24h, LDR-48h and LDR-72h groups were all statistically significantly different from S group. The expression of EGFR and VEGFR also decreased, and LDR-24h group was the lowest (P 〈 0.05). Conclusion: Seventy-two h after low-dose total body irradiation, there was no significant change in tumor size of mice bearing S180 sarcoma. Low-dose total body radiation decreased the expression of PCNA inhibiting tumor growth; reduced the expression of EGFR in tumor tissue impacting the signal transduction of tumor cells. The study also indicated that low-dose total body irradiation, within a certain period of time, can decrease the expression of hypoxia factor EPO and VEGFR, which may improve the situation of tumor hypoxia and radiosensitivity of tumor itself.
基金a Project for Nuclear Military Personal Health Assessment and Radiation Damage Treat-ment, No. 616010305
文摘BACKGROUND: Bone marrow-derived mesenchymal stem cells (BMSCs) are a potentially useful source for cell replacement therapy following spinal cord injury. However, the homing characteristics of BMSCs in vivo remain unclear. Low-dose radiation has been shown to promote homing of BMSCs to exposed sites. OBJECTIVE: To investigate the effects of low-dose local radiation to non-injured areas on the ability of human BMSCs to home to the injured mouse spinal cord, as well as recovery of spinal cord injury. DESIGN, TIME AND SE'I-FING: A randomized, controlled, animal experiment was performed at the Central Laboratory, Second Affiliated Hospital of Soochow University between October 2007 and October 2008. MATERIALS: BMSCs were isolated from four adult, human donors. METHODS: Fifty adult, female, Balb/c mice were subjected to adjusted weight-drop impact resulting in complete paraplegia. Three days later, mice were randomly assigned to a radiation + transplantation group (n = 23) and a transplantation group (n = 20). In total, 2 x 106 carboxyfluorescein diacetate succinimidyl ester-labeled BMSCs were injected into each mouse via the caudal vein. Mice in the radiation + transplantation group received 2.5 Gy local X-ray irradiation 2 hours before BMSCs injection. MAIN OUTCOME MEASURES: The homing of BMSCs to injured cord and irradiated skin after transplantation was observed by fluorescence microscope; the structure recovery of injured cord was assessed by magnetic resonance imaging. RESULTS: Compared with the transplantation group, at 24 hours after transplantation, the number of BMSCs was significantly increased in the injured area and the exposed site (P 〈 0.05), and inflammation and edema were significantly alleviated in the injured cord in the radiation + transplantation group. CONCLUSION: Local low-dose radiation has the potential to promote homing of BMSCs and recovery of spinal cord injury, although the radiated region was not injured area.
基金supported by the Natural Science Foundation of Hubei Province,China(No.2012FKB02443)
文摘The influence of low tube voltage in dual source CT(DSCT) coronary artery imaging on image quality and radiation dose and its application value in clinical practice were investigated. Totally, 300 cases of chest pain with low body mass index(BMI 〈18.5 kg/m2) subjected to DSCT coronary artery imaging were prospectively enrolled. The heart rate in all patients were greater than 65/min. The retrospective ECG gated scanning mode and simple random sampling method were used to assign the patients into groups A, B and C(n=100 each). The patients in groups A, B and C experienced 120-, 100-, and 80-kV tube voltage imaging respectively, and the image quality was evaluated. The CT volume dose index(CTDIvol) and dose length product(DLP) were recorded, and the effective dose(ED) was calculated in each group. The image quality scores and radiation doses in groups were compared, and the influence of tube voltage on image quality and radiation dose was analyzed. The results showed that the excellent rate of image quality in groups A, B and C was 95.69%, 94.72% and 96.33% respectively with the difference being not statistically significant among the three groups(P〉0.05). The CTDIvol values in groups A, B and C were 51.35±12.21, 21.28±7.13 and 6.34±3.34 mGy, respectively, with the difference being statistically significant(P〈0.05). The ED values in groups A, B and C were 9.27±1.63, 4.56±2.29 and 2.29±1.69 mSv, respectively, with the difference being statistically significant(P〈0.05). It was suggested that for the patients with low BMI, the application of DSCT coronary artery imaging with low tube voltage can obtain satisfactory image quality, and simultaneously, significantly reduce the radiation dose.
基金National Natural Science Foundation of China,No.NSFC 81171389Key Program of Basic Research from Shanghai Municipal Science and Technology Commission,No.12JC1406500the Program of Shanghai Municipal Health Outstanding Discipline Leader,No.XBR 2013110
文摘AIM:To evaluate the feasibility of low contrast medium and radiation dose for hepatic computed tomography(CT) perfusion of rabbit VX2 tumor.METHODS:Eleven rabbits with hepatic VX2 tumor underwent perfusion CT scanning with a 24-h interval between a conventional tube potential(120 k Vp) protocol with 350 mg I/m L contrast medium and filtered back projection,and a low tube potential(80 k Vp) protocol with 270 mg I/m L contrast medium with iterative reconstruction.Correlation and agreement among perfusion parameters acquired by the conventional and low dose protocols were assessed for the viable tumor component as well as whole tumor.Image noise and tumor-to-liver contrast to noise ratio during arterial and portal venous phases were evaluated.RESULTS:A 38% reduction in contrast medium dose(360.1 ± 13.3 mg I/kg vs 583.5 ± 21.5 mg I/kg,P < 0.001) and a 73% decrease in radiation dose(1898.5 m Gy·cm vs 6951.8 m Gy·cm) were observed.Interestingly,there was a strong positive correlation in hepatic arterial perfusion(r = 0.907,P < 0.001;r = 0.879,P < 0.001),hepatic portal perfusion(r = 0.819,P = 0.002;r = 0.831,P = 0.002),and hepatic blood flow(r = 0.945,P < 0.001;r = 0.930,P < 0.001) as well as a moderate correlation in hepatic perfusion index(r = 0.736,P = 0.01;r = 0.636,P = 0.035) between the low dose protocol with iterative reconstruction and the conventional protocol for the viable tumor component and the whole tumor.These two imaging protocols provided a moderate but acceptable agreement for perfusion parameters and similar tumorto-liver CNR during arterial and portal venous phases(5.63 ± 2.38 vs 6.16 ± 2.60,P = 0.814;4.60 ± 1.27 vs 5.11 ± 1.74,P = 0.587).CONCLUSION:Compared with the conventional protocol,low contrast medium and radiation dose with iterative reconstruction has no significant influence on hepatic perfusion parameters for rabbits VX2 tumor.
基金This work was supported by a grant from NSFC (No.39570188)
文摘WT5”BZ] To study the molecular mechanism of the stimulatory effect of low dose radiation(LDR) on T cell activation. [WT5”BX]Methods.[WT5”BZ] Thymocytes from Kunming mice exposed to whole body irradiation(WBI) with different doses of X rays were analyzed for the changes in signal molecules of the phospholipase C phosphatidylinositol biphosphate(PLC IP2) and G protein adenylate cyclase(AC) pathways. [WT5”BX]Results.[WT5”BZ]It was found that[Ca 2+ ] i increased in response to doses within 0 2 Gy which was most marked after 0 075 Gy and the increase was accentuated in the presence of Con A. The changes in CD3 and calcineurin(CN) expression of the thymocytes followed the same pattern as the alterations in [Ca 2+ ] i after LDR. The expression of α,β1 and β2 isoforms of protein kinase C(PKC) was all up regulated after 0 075 Gy with the increase in PKC β1 expression being most marked. The cAMP/cGMP ratio and PKA activity of the thymocytes was lowered after low dose radiation and increased after doses above 0 5 Gy in a dose dependent manner, thus giving rise to J shaped dose response curves. The Ca antagonist TMB 8 and cAMP stimulant cholera toxin suppressed the augmented thymocyte proliferation induced by LDR. [WT5”BX]Conclusion.[WT5”BZ]Data presented in the present paper suggest that activation of the PLC PIP2 signal pathway and suppression of the AC cAMP signal pathway are involved in the stimulation of the thymocytes following WBI with low dose X rays.
文摘Human lymphocytes pre-exposed to 10 mGy or 50 mGy of X-rays become less sensitive to subsequent large dose irradiation, exhibited lower rate of chromosome aberration than expected. This adaptive response could be inhibited by cycloheximide, a protein synthesis inhibitor for successive 2 h period ranging from 0.5h before to 4h after the low dose exposure, indicating that the adaptive response was directly related with the protein synthesis.
文摘It is first reported in the present paper that whole-body irradiation (WBI) with low dose X-rays could increase intracellular calcium ions ([Ca2+]i) and stimulate protein kinase C (PKC) activity of mouse lymphocytes. Following WBI of male Kunming micc With 75 mGy X-rays at a dose rate of 12.5 mGy/min the mobilization of [Ca2+]i with Con A in CD4+ and CD8+ Cells in the thymus and spleen was potentiated and the amplitude of [Ca2+], mobilization in thymocytes in response to anti-CD3 monoclonal antibody increased with time from 4 to 24 h following low dose radiation. The PKC activity in the homogenate of spleen was markedly stimulated 12 h after WBl with 75 mGy, reaching its peak value at 24-48 h and coming down to lower than normal on day 7. However, the PKC activity in the separated T lymphocytes reached its peak value at 12 h and that in the B lymphocytes reached its peak value on day 4, both coming down to below control on day 7. The implications of this facilitation of signal transduction in T lymphocytes in the mechanism of immunoenhancement after low dose radiation were discussed
基金Supported by a grant from the Province Natural Sciences Foundation of Shandong(No.ZR2016040034)
文摘Objective To investigate the mechanism of low-dose fractionated radiation on reversing cisplatin resistance in ovarian carcinoma via vascular endothelial growth factor(VEGF) and mammalian target of rapamycin(mTOR) in vivo.Methods Human cisplatin-resistant ovarian carcinoma cells(SKOV3/DDP) were injected into nude mice to establish ovarian cancer xenografts. The mice were randomly divided into three groups: a control group, a low-dose fractionated radiation(LDRFT) group, and a conventional-dose radiation group. Each group was exposed to 0 cGy, 50 cGy, and 200 cGy radiation, respectively, for 4 weeks, up to a total of 8.0 Gy. Mice in the LDFRT group were irradiated twice daily with 6 hour intermissions on day 1 and 2 of every week for a total of 4 weeks. Conventional-dose group mice were given a single 200 cGy radiation dose on the first day each week for a total of 4 weeks. Maximum horizontal and vertical diameters of the tumors were measured every other day and used to create a tumor growth curve. After 4 weeks of irradiation, we dissected the tumor tissue and calculated the tumor inhibition rate. RT-PCR detected the expression of VEGF and m TOR, and Western blots detected the expression of corresponding proteins.Results Both LDRFT and conventional-dose radiation inhibited the growth of tumor cells, and growth of tumors in the two radiation groups compared with growth in the control group were significantly different(P < 0.05). The rate of tumor inhibition in the LDFRT group(37.5603%) was lower than in the conventionaldose group(47.4446%), but there was no significant difference(P 0.05). Compared with the other two groups, the m RNA expression of VEGF was significantly lower in the LDFRT group(P < 0.05), but there was no obvious difference between the conventional-dose and control groups. There was no obvious difference in the m RNA expression of m TOR among the three groups, but the expression of the protein p-m TOR was lower in the LDFRT group(P < 0.05), as confirmed by Western blotting.Conclusion LDFRT is as effective at inhibiting the growth of tumor cells as conventional-dose radiation. In addition, LDFRT could deregulate the expression of VEGF and p-m TOR, and may therefore play a vital role in reversing cisplatin resistance in ovarian cancer.
文摘This work was supported by the National Natural Science Foundation of China (No. 3870902). Objective: To determine the NK activity of lymphocyte subsets and the effects of low dose radiation. Methods: Lymphocyte subsets were separated by monoclonal antibodies. The NK activity of each subset on tumor cells was detected by radioactive release method. Results: The results showed that besides NK cells, CD 4, CD 8 and B cells alone can kill tumor cells. But the cellkilling activity of NK cells appeared to be strongest. There was synergistic effect between CD 4 and NK cells. The activity of mixed lymphocytes was more than that of only one subset. The effect of low dose radiation (LDR) on NK activity of panlymphocytes or NK cells was different. Conclusion: This paper demonstrated that NK activity of mononuclear cells was called “NK activity of lymphocytes”, but it is not true. Only when NK cells were separated by monoclonal antibodies, its killer activity can be called “activity of NK cells”.
文摘It is represented the review about the effect of low doses of ionized radiation on different types of biological objects (Japanese quail embryos, Aspergillus niger, Spirostomum ambiguum Ehrbg., mezenchim stem cells of mice bone brain, dry seeds of the highest plants, blood lymphocytes of pilots and cosmonauts) and water medium. In model experiments under the chronic ionized radiation in doses comparable with the doses of ionized radiation inside the orbital space stations and during the flight in interplanetary space was shown alike with morphological deviations (Japanese quail embryos, Aspergillus niger), the phenomenon of radiation hormezis (Aspergillus niger, mezenchim stem cells), the increasing of the germination of seeds, the decreasing of spontaneous motion activity of spirostoms and DNA damage, chromosome aberrations and the increased radio-sensitivity to adding radiation load in blood lymphocytes. These data testified the fact that the definite factor of ionized radiation effect is the changing of water medium state. Thus under the interplanetary cosmic flight and long stay on the orbit in the region of magnetosphere the studying kinds of radiation first effected on the water medium of organism as a result morpho-functional structures were changed.
文摘Objective: The aim of this study was to explore the effect of low dose radiation on cytokine excreted by mice inbreathing of atomization of PYM. Methods: Kunming male mice were randomly divided into three groups: blank group, PYM group (P group), low dose radiation + PYM group (P + L group). Mice of P + L group were given whole body low dose radiation 75 mGY, dose rate were 12.5 mGY/min. After 6 h, mice in both P + L group and P group were given inbreathe of atomization of PYM, concentration was 2 mg/mL. Mice were sacrificed after the dl, d7, d14, d21 and d28, IL-6 were detected in alveolar irrigating solution. The tissue samples of mice lung were fixed in 10% formalin, TNF-α and TGF-β were analyzed by immuno- histochemistry. Results: Compared with P group, IL-6 in low dose radiation + PYM group were lower, near to blank group, the difference had notable statistical significance on the dl and the d7, while on the d14, d21, d28, the difference had not statisti- cal significance. It suggested that low dose radiation could reduce the resection of IL-6 at the begin of lung injure induced by low dose radiation. The expression of TGF-β and TNF-α in P + L group were lower than that in P group, but the difference in the two groups had statistical significance by gray analysis P 〈 0.05. Conclusion: In the early stage of lung injure caused by PYM in mice, low dose radiation of 75 mGY can reduce the secretion of IL-6, decrease the production of TGF-β and TNF-α.