低剂量辐射超敏感性的分子机制及临床应用进展
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摘要
全文对近年来低剂量辐射超敏感性(low dose hyper-radiosensitivity,HRS)的体内及体外实验,从细胞周期调控、细胞凋亡、DNA损伤修复、辐射诱导的旁观者效应等四个方面的分子机制进行探讨,并对HRS临床意义进行阐述和展望,以期为临床研究提供参考。
The review article discusses the low dose hyper-radiosensitivity(HRS)in vivo and in vitro experiments. The molecular mechanisms of HRS are discussed from four aspects:cell cycle control,cell apoptosis,DNA repair and radiation-induced bystander effect. In addition,the clinical significance of HRS is described and prospected in order to provide reference for clinical research.
The review article discusses the low dose hyper-radiosensitivity(HRS)in vivo and in vitro experiments. The molecular mechanisms of HRS are discussed from four aspects:cell cycle control,cell apoptosis,DNA repair and radiation-induced bystander effect. In addition,the clinical significance of HRS is described and prospected in order to provide reference for clinical research.
引文
[1]Marples B,Collis SJ.Low-dose hyper-radiosensitivity:past,present,and future[J].Int J Radiat Oncol Biol Phys,2008,70(5):1310-1318.
[2]Dai X,Tao D,Wu H,et al.Low dose hyper-radiosensitivity in human lung cancer cell line A549 and its possible mechanisms[J].J Huazhong Univ Sci Technolog Med Sci,2009,29(1):101-106.
[3]Slonina D,Gasinska A,Biesage B,et al.An association between low dose hyper radiosensitivity and the early G2-phase checkpoint in normal fibroblasts of cancer patients[J].DNA Repair(Amst),2016,39:41-45.
[4]Chen QT,Cheng J.Studies on the correlation between early G2checkpoint and low dose radiosensitivity or enhanced radioresistance[J].Chinese Journal of Radiation Oncogy,2012,21(4):402-404.[陈其田,程晶.早期G2期检查点与细胞低剂量放射敏感性或增强的放射抗性现象相关性研究进展[J].中华放射肿瘤学杂志,2012,21(4):402-404.]
[5]Krueger SA,Collis SJ,Joiner MC,et al.The transition in survivalfrom low-dose hyper-radiosensitivity to increased radioresistanceis independent of activation of ATMSER1981 activity[J].Int J Radiat Oncol Biol Phys,2007,69(4):1262-1271.
[6]Gupta S,Koru-Sengul T,Arnold SM,et al.Low-dose fractionated radiation potentiates the effects of cisplatin independent of the hyper-radiation sensitivity in human lung cancer cells[J].Mol Cancer Ther,2011,10(2):292-302.
[7]Landsverk KS,Patzke S,Rein ID,et al.Three independent mechanisms for arrest in G2after ionizing radiation[J].Cell Cycle,2011,10(5):819-829.
[8]Short SC,Bourne S,Martindale C,et al.DNA damage responses at low radiation doses[J].Radiat Res,2005,164(3):292-302.
[9]Wykes SM,Piasentin E,Joiner MC,et al.Low-dose hyperradiosensitivityis not caused by a failure to recognize DNAdouble-strand breaks[J].Radiat Res,2006,165(5):516-524.
[10]Tao D,Cheng J.Research progress of low dose radiation hypersensitivity molecular mechanism[J].Cancer Reserch on Prevention And Treatment,2008,35(5):367-370.[陶丹,程晶.低剂量辐射超敏感性分子机制的研究进展[J].肿瘤防治研究,2008,35(5):367-370.]
[11]Enns L,Bogen KT,Wizniak J,et al.Low-dose radiation hypersensitivity is associated with p53-dependent apoptosis[J].Mol Cancer Res,2004,2(10):557-560.
[12]Krueger SA,Joiner MC,Weinfeld M,et al.Role of apoptosis inlow-dose hyper-radiosensitivity[J].Radiat Res,2007,167(3):260-267.
[13]Kang YH,Wang ZM.Research progress of radiation induced bystander effect and clinical significance[J].Chin JClinicians(Electronic Edition),2013,7(22):10329-10332.[康亚辉,王忠明.放射诱导旁观者效应研究进展及临床意义[J].中华临床医师杂志,2013,7(22):10329-10332.]
[14]Fernandez-Palomo C,Seymour C,Mothersill C.Inter-relationship between low-dose hyper-radiosensitivity and radiation-induced bystander effects in the human T98Gglioma and the epithelial HaCaT cell line[J].Radiat Res,2016,185(2):124-133.
[15]Nuta O,Darroudi F.The impact of the bystander effect on the lowdosehypersensitivity phenomenon[J].Radiat Environ Biophys,2008,47(2):265-274.
[16]Kalanxhi E,Dahle J.The role of serotonin and p53 status in theradiation-induced bystander effect[J].Int J Radiat Biol,2012,88(10):773-776.
[17]Martin LM,Marples B,Lynch TH,et al.Exposure to low dose ionising radiation:Molecularand clinical consequences[J].Cancer Lett,2013,338(2):209-218.
[18]HonoréHB,Bentzen SM.A modelling study of the potential influenceof low dose hypersensitivity on radiation treatmentplanning[J].Radiother Oncol,2006,79(1):115-121.
[19]Lin PS,Wu A.Not all 2 Gray radiation prescriptions are equivalent:Cytotoxic effect depends on delivery sequences of partialfractionated doses[J].Int J Radiat Oncol Biol Phys,2005,63(2):536-544.
[20]Krause M,Prager J,Wohlfarth J,et al.Ultrafractionation doesnot improve the results of radiotherapy in radioresistant murineDDL1 lymphoma[J].Strahlenther Onkol,2005,181(8):540-544.
[21]Krause M,Hessel F,Wohlfarth J,et al.Ultrafractionation in A7human malignant glioma in nude mice[J].Int J Radiat Biol,2003,79(6):377-383.
[22]ToméWA,Howard SP.On the possible increase in local tumour control probability for gliomas exhibiting low dose hyper-radiosensitivity using a pulsed schedule[J].Br JRadiol,2007,80(949):32-37.
[23]Lee DY,Chunta JL,Park SS,et al.Pulsed versus conventional radiation therapy in combination with temozolomide in a murine orthotopic model of glioblastoma multiforme[J].Int J Radiat Oncol Biol Phys,2013,86(5):978-985.
[24]Dilworth JT,Krueger SA,Dabjan M,et al.Pulsed low-dose irradiation of orthotopic glioblastoma multiforme(GBM)in a pre-clinical model:effects on vascularization and tumor control[J].Radiother Oncol,2013,108(1):149-154.
[25]Richards GM,Tome WA,Robins HI,et al.Pulsed reduced dose-rate radiotherapy:a novel locoregional retreatment strategy for breast cancer recurrence in the previously irradiated chest wall,axilla,or supraclavicular region[J].Breast Cancer Res Treat,2009,114(2):307-313.
[26]Zhang P,Wang B,Chen X,et al.Local Tumor control and norreal tissue toxicity of pulsed low-dose rate radiotherapy for recurrent lung cancer:An in vivo animal study[J].Dose Response,2015,13(2):1-9.
[27]Wei X,Du J,Yang Y,et al.Treatment of 1 cases of hilar lymph node metastasis of gastric cancer with pulsed low dose rate radiotherapy[J].Chinese Clinical Oncology,2017,22(7):670-672.[韦笑,杜娟,杨阳,等.脉冲式低剂量率放疗治疗胃癌肝门部淋巴结转移1例[J].临床肿瘤学杂志,2017,22(7):670-672.]
[2]Dai X,Tao D,Wu H,et al.Low dose hyper-radiosensitivity in human lung cancer cell line A549 and its possible mechanisms[J].J Huazhong Univ Sci Technolog Med Sci,2009,29(1):101-106.
[3]Slonina D,Gasinska A,Biesage B,et al.An association between low dose hyper radiosensitivity and the early G2-phase checkpoint in normal fibroblasts of cancer patients[J].DNA Repair(Amst),2016,39:41-45.
[4]Chen QT,Cheng J.Studies on the correlation between early G2checkpoint and low dose radiosensitivity or enhanced radioresistance[J].Chinese Journal of Radiation Oncogy,2012,21(4):402-404.[陈其田,程晶.早期G2期检查点与细胞低剂量放射敏感性或增强的放射抗性现象相关性研究进展[J].中华放射肿瘤学杂志,2012,21(4):402-404.]
[5]Krueger SA,Collis SJ,Joiner MC,et al.The transition in survivalfrom low-dose hyper-radiosensitivity to increased radioresistanceis independent of activation of ATMSER1981 activity[J].Int J Radiat Oncol Biol Phys,2007,69(4):1262-1271.
[6]Gupta S,Koru-Sengul T,Arnold SM,et al.Low-dose fractionated radiation potentiates the effects of cisplatin independent of the hyper-radiation sensitivity in human lung cancer cells[J].Mol Cancer Ther,2011,10(2):292-302.
[7]Landsverk KS,Patzke S,Rein ID,et al.Three independent mechanisms for arrest in G2after ionizing radiation[J].Cell Cycle,2011,10(5):819-829.
[8]Short SC,Bourne S,Martindale C,et al.DNA damage responses at low radiation doses[J].Radiat Res,2005,164(3):292-302.
[9]Wykes SM,Piasentin E,Joiner MC,et al.Low-dose hyperradiosensitivityis not caused by a failure to recognize DNAdouble-strand breaks[J].Radiat Res,2006,165(5):516-524.
[10]Tao D,Cheng J.Research progress of low dose radiation hypersensitivity molecular mechanism[J].Cancer Reserch on Prevention And Treatment,2008,35(5):367-370.[陶丹,程晶.低剂量辐射超敏感性分子机制的研究进展[J].肿瘤防治研究,2008,35(5):367-370.]
[11]Enns L,Bogen KT,Wizniak J,et al.Low-dose radiation hypersensitivity is associated with p53-dependent apoptosis[J].Mol Cancer Res,2004,2(10):557-560.
[12]Krueger SA,Joiner MC,Weinfeld M,et al.Role of apoptosis inlow-dose hyper-radiosensitivity[J].Radiat Res,2007,167(3):260-267.
[13]Kang YH,Wang ZM.Research progress of radiation induced bystander effect and clinical significance[J].Chin JClinicians(Electronic Edition),2013,7(22):10329-10332.[康亚辉,王忠明.放射诱导旁观者效应研究进展及临床意义[J].中华临床医师杂志,2013,7(22):10329-10332.]
[14]Fernandez-Palomo C,Seymour C,Mothersill C.Inter-relationship between low-dose hyper-radiosensitivity and radiation-induced bystander effects in the human T98Gglioma and the epithelial HaCaT cell line[J].Radiat Res,2016,185(2):124-133.
[15]Nuta O,Darroudi F.The impact of the bystander effect on the lowdosehypersensitivity phenomenon[J].Radiat Environ Biophys,2008,47(2):265-274.
[16]Kalanxhi E,Dahle J.The role of serotonin and p53 status in theradiation-induced bystander effect[J].Int J Radiat Biol,2012,88(10):773-776.
[17]Martin LM,Marples B,Lynch TH,et al.Exposure to low dose ionising radiation:Molecularand clinical consequences[J].Cancer Lett,2013,338(2):209-218.
[18]HonoréHB,Bentzen SM.A modelling study of the potential influenceof low dose hypersensitivity on radiation treatmentplanning[J].Radiother Oncol,2006,79(1):115-121.
[19]Lin PS,Wu A.Not all 2 Gray radiation prescriptions are equivalent:Cytotoxic effect depends on delivery sequences of partialfractionated doses[J].Int J Radiat Oncol Biol Phys,2005,63(2):536-544.
[20]Krause M,Prager J,Wohlfarth J,et al.Ultrafractionation doesnot improve the results of radiotherapy in radioresistant murineDDL1 lymphoma[J].Strahlenther Onkol,2005,181(8):540-544.
[21]Krause M,Hessel F,Wohlfarth J,et al.Ultrafractionation in A7human malignant glioma in nude mice[J].Int J Radiat Biol,2003,79(6):377-383.
[22]ToméWA,Howard SP.On the possible increase in local tumour control probability for gliomas exhibiting low dose hyper-radiosensitivity using a pulsed schedule[J].Br JRadiol,2007,80(949):32-37.
[23]Lee DY,Chunta JL,Park SS,et al.Pulsed versus conventional radiation therapy in combination with temozolomide in a murine orthotopic model of glioblastoma multiforme[J].Int J Radiat Oncol Biol Phys,2013,86(5):978-985.
[24]Dilworth JT,Krueger SA,Dabjan M,et al.Pulsed low-dose irradiation of orthotopic glioblastoma multiforme(GBM)in a pre-clinical model:effects on vascularization and tumor control[J].Radiother Oncol,2013,108(1):149-154.
[25]Richards GM,Tome WA,Robins HI,et al.Pulsed reduced dose-rate radiotherapy:a novel locoregional retreatment strategy for breast cancer recurrence in the previously irradiated chest wall,axilla,or supraclavicular region[J].Breast Cancer Res Treat,2009,114(2):307-313.
[26]Zhang P,Wang B,Chen X,et al.Local Tumor control and norreal tissue toxicity of pulsed low-dose rate radiotherapy for recurrent lung cancer:An in vivo animal study[J].Dose Response,2015,13(2):1-9.
[27]Wei X,Du J,Yang Y,et al.Treatment of 1 cases of hilar lymph node metastasis of gastric cancer with pulsed low dose rate radiotherapy[J].Chinese Clinical Oncology,2017,22(7):670-672.[韦笑,杜娟,杨阳,等.脉冲式低剂量率放疗治疗胃癌肝门部淋巴结转移1例[J].临床肿瘤学杂志,2017,22(7):670-672.]