摘要
为了探讨不同剂量电离辐射及其所致条件培养基对肺癌相关骨髓间充质干细胞(bone marrowmesenchymal stemcells,BMMSCs)基因组不稳定性的影响,以A549和人BMMSCs为研究对象,采用X射线辐射和条件培养基转移的方法建立辐射旁效应模型,检测基因组不稳定性相关的细胞克隆存活率、微核率、53BP1(tumor suppressor p53 binding protein 1)焦点数等指标,同时采用ELISA法检测旁效应条件培养液不同时间点ROS、NO、TGF-β1的水平。结果显示:与正常BMMSCs组相比,IR组、A549-medium组和BMMSCs-medium组的细胞增殖均减少(P<0.05);细胞微核率和53BP1焦点数均增多(P<0.05);IR组变化最明显,其次为A549-medium组。此外,A549-medium组中TGF-β1、ROS以及NO的水平与BMMSCs-medium组相比均显著升高(P<0.05)。实验结果初步表明,辐射可能通过条件培养基中ROS、TGF-β1、NO等分子诱导未照射BMMSCs产生类似于直接辐射造成的基因不稳定性旁损伤效应,并且A549-medium组的旁损伤强于BMMSCs-medium组。
To explore the effects of different doses of ionizing radiation and conditioned mediums on genomic instability of bone marrow mesenchymal stem cells(BMMSCs)associated with lung cancer,A549 cells and human BMMSCs were taken as research objects,and a model of the radiation-induced bystander effect was established by X-ray radiation and conditioned medium transfer.Cell colony survival rate,micronucleus rate and the number of foci induced by 53BP1 were detected.ELISA was used to detect the levels of ROS,NO and TGF-β1 in conditioned mediums at different time points.The results showed that cell proliferation in IR group,A549-medium group and BMMSCs-medium group decreased(P<0.05),and that the cell micronucleus rate and the number of 53BP1 foci increased(P<0.05).The most obvious change was observed in IR group,followed by A549-medium group.The levels of TGF-β1,ROS and NO in A549-medium group were significantly higher than those in BMMSCs-medium group(P<0.05).The experiments indicated that radiation might induce gene instability effect in non-irradiated BMMSCs through ROS,TGF-β1 and NO in the conditioned medium.This effect was similar to injury caused by direct radiation.A549-medium group had a stronger bystander injury than BMMSCs-medium group.
作者
张利英
张苡铭
周妮娜
卢志伟
丁楠
华君瑞
李洋洋
周婷
刘颖
刘永琦
ZHANG Li-ying;ZHANG Yi-ming;ZHOU Ni-na;LU Zhi-wei;DING Nan;HUA Jun-rui;LI Yang-yang;ZHOU Ting;LIU Ying;LIU Yong-qi(Provincial-level Key Laboratory for Molecular Medicine of Major Diseases and the Prevention and Treatment with Traditional Chinese Medicine Research in Gansu Colleges and Universities,Gansu University of Chinese Medicine,Lanzhou 730000,Gansu,China;Key Laboratory of Space Radiobiology of Gansu Province&CAS Key Laboratory of Heavy Ion Radiation Biology and Medicine,Institute of Modern Physics,Chinese Academy of Sciences,Lanzhou 730000,Gansu,China;Emergency Department,Affiliated Hospital of Gansu University of Chinese Medicine,Lanzhou 730000,Gansu,China;Key Laboratory of Dunhuang Medicine and Transformation at Provincial and Ministerial Level,Gansu University of Chinese Medicine,Lanzhou 730000,Gansu,China)
出处
《生命科学研究》
CAS
CSCD
2021年第2期117-123,共7页
Life Science Research
基金
国家自然科学基金资助项目(82004094,81973595)
甘肃省自然科学基金项目(20JR10RA318)
陇原青年创新创业人才项目(2021-1)
甘肃省中药药理与毒理实验室开放基金项目(zyzx-2020-18)。
