Pavlova Galina, Belyashova Alexandra, Savchenko Ekaterina, Panteleev Dmitri, Shamadykova Dzhirgala, Nikolaeva Anna, Pavlova Svetlana, Revishchin Alexander, Golbin Denis, Potapov Alexander, Antipina Natalia, Golanov Andrey
Nikolay Nilovich (N.N.) Burdenko National Medical Research Center of Neurosurgery (NMRCN), Moscow, Russia.
Laboratory of Neurogenetics and Genetics Development, Institute of Higher Nervous Activity and Neurophysiology of Russian Academy of Sciences, Moscow, Russia.
Front Oncol. 2022 Aug 4;12:912741. doi: 10.3389/fonc.2022.912741. eCollection 2022.
Radiation therapy induces double-stranded DNA breaks in tumor cells, which leads to their death. A fraction of glioblastoma cells repair such breaks and reinitiate tumor growth. It was necessary to identify the relationship between high radiation doses and the proliferative activity of glioblastoma cells, and to evaluate the contribution of DNA repair pathways, homologous recombination (HR), and nonhomologous end joining (NHEJ) to tumor-cell recovery. We demonstrated that the GO1 culture derived from glioblastoma cells from Patient G, who had previously been irradiated, proved to be less sensitive to radiation than the Sus\fP2 glioblastoma culture was from Patient S, who had not been exposed to radiation before. GO1 cell proliferation decreased with radiation dose, and MTT decreased to 35% after a single exposure to 125 Gγ. The proliferative potential of glioblastoma culture Sus\fP2 decreased to 35% after exposure to 5 Gγ. At low radiation doses, cell proliferation and the expression of RAD51 were decreased; at high doses, cell proliferation was correlated with Ku70 protein expression. Therefore, HR and NHEJ are involved in DNA break repair after exposure to different radiation doses. Low doses induce HR, while higher doses induce the faster but less accurate NHEJ pathway of double-stranded DNA break repair.
放射治疗会在肿瘤细胞中诱导双链DNA断裂,从而导致肿瘤细胞死亡。一部分胶质母细胞瘤细胞会修复此类断裂并重新启动肿瘤生长。有必要确定高辐射剂量与胶质母细胞瘤细胞增殖活性之间的关系,并评估DNA修复途径、同源重组(HR)和非同源末端连接(NHEJ)对肿瘤细胞恢复的作用。我们证明,来自先前接受过放疗的患者G的胶质母细胞瘤细胞系GO1,比来自未曾接受过放疗的患者S的Sus\fP2胶质母细胞瘤细胞系对辐射的敏感性更低。GO1细胞的增殖随辐射剂量降低,单次暴露于125 Gγ后MTT降至35%。胶质母细胞瘤细胞系Sus\fP2暴露于5 Gγ后增殖潜力降至35%。在低辐射剂量下,细胞增殖和RAD51的表达降低;在高剂量下,细胞增殖与Ku70蛋白表达相关。因此,HR和NHEJ参与了不同辐射剂量照射后的DNA断裂修复。低剂量诱导HR,而高剂量诱导双链DNA断裂修复中更快但准确性更低的NHEJ途径。