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首页> 外文期刊>Radiotherapy and oncology: Journal of the European Society for Therapeutic Radiology and Oncology >Radiocontrast media affect radiation-induced DNA damage repair in vitro and in vivo by affecting Akt signalling.
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Radiocontrast media affect radiation-induced DNA damage repair in vitro and in vivo by affecting Akt signalling.

机译:放射性对比剂介质通过影响Akt信号传导在体外和体内影响辐射诱导的DNA损伤修复。

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PURPOSE: The study was performed to investigate cytogenetic effects of ionic and non-ionic radiocontrast media (RCM) meglumine, iohexol alone and in combination with irradiation in mouse bone marrow cells in vivo and in vitro. MATERIALS AND METHODS: Micronuclei assay was performed in bone marrow cells (BMC) of Balb/C mice intraperitoneally injected with RCM in the presence or absence of whole-body irradiation of 50 mGy. DNA repair (NHEJ) signalling and efficiency were analyzed by Western blot and gammaH2AX-foci assay in normal fibroblast HSF-7 and HUVEC cells. RESULTS: Both compounds reduced proliferation of BMC significantly. Concentrations of 0.5, 1 and 2 ml/kg meglumine or iohexol significantly enhanced the frequency of micronucleated polychromatic erythrocytes (MnPCEs) at all doses of meglumine (p<0.01) and 2 ml/kg of iohexol (p<0.05). Combined with irradiation meglumine at 0.5 and 1 ml/kg led to a higher frequency of MnPCEs than iohexol/IR (p<0.05). Meglumine induced DNA-double strand breaks (DNA-DSB) in non-irradiated HSF and strongly increased residual DNA-DSB within 10 min to 24h after irradiation with 200 or 400 mGy (p<0.001). Iohexol did not induce DNA-DSB but blocked repair of radiation-induced DNA-DSB significantly (p<0.05). Meglumine blocked IR-induced Akt phosphorylation, phosphorylation of DNA-PKcs (S2056, T2609) and ATM (S1981). Iohexol only blocked phosphorylation of Akt and DNA-PKcs at S2056. CONCLUSION: RCM result in clastogenic effects through interference intracellular signalling cascades involved in the regulation of non-homologous end-joining repair of DNA-DSB.
机译:目的:进行这项研究以研究离子和非离子放射性造影剂(RCM)葡甲胺,碘海醇单独使用以及联合照射在体内和体外对小鼠骨髓细胞的细胞遗传学作用。材料与方法:在存在或不存在50 mGy全身照射的情况下,在腹膜内注射RCM的Balb / C小鼠的骨髓细胞(BMC)中进行微核分析。在正常成纤维细胞HSF-7和HUVEC细胞中,通过蛋白质印迹和gammaH2AX病灶分析法分析了DNA修复(NHEJ)信号传导和效率。结果:两种化合物均能显着降低BMC的增殖。在所有剂量的葡甲胺(p <0.01)和2 ml / kg碘海醇(p <0.05)下,0.5、1和2 ml / kg葡甲胺或碘海醇的浓度均显着提高了微核多色红细胞(MnPCE)的频率。结合0.5和1 ml / kg的葡甲胺照射导致MnPCE的频率高于碘海醇/IR(p<0.05)。在接受200或400 mGy照射后的10分钟至24小时内,葡甲胺诱导的非照射HSF中的DNA双链断裂(DNA-DSB)大大增加了残留DNA-DSB(p <0.001)。碘海醇不诱导DNA-DSB,但显着阻断辐射诱导的DNA-DSB的修复(p <0.05)。葡甲胺可阻断IR诱导的Akt磷酸化,DNA-PKcs(S2056,T2609)和ATM(S1981)的磷酸化。碘海醇仅在S2056处阻断Akt和DNA-PKcs的磷酸化。结论:RCM通过干扰细胞内信号转导级联作用而导致杀伤作用,该级联作用涉及DNA-DSB的非同源末端连接修复的调控。

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