【摘要】 目的探讨不同照射剂量对BRCA基因突变及BRCA基因非突变的乳腺癌细胞DNA损伤和凋亡的影响。方法BRCA基因突变的乳腺癌细胞株MDA-MB-436及BRCA基因非突变的乳腺癌细胞株MDA-MB-231分别按0 Gy、2 Gy、4 Gy、6 Gy、8 Gy、10 Gy照射剂量进行X射线照射。以流式细胞术仪检测细胞凋亡率,在各照射剂量中,取γH2AX免疫荧光焦点最明显的时间点(30 min)检测细胞DNA双链损伤情况。结果乳腺癌细胞DNA损伤及细胞凋亡率均随照射剂量增加而加重,8 Gy照射剂量时两个细胞株的DNA损伤及细胞凋亡率均达到最高,MDA-MB-436细胞分别为(47±1.802)个和(21.245±1.325)%,MDA-MB-231细胞分别为(45±1.779)个和(19.220±1.220)%。不同照射剂量下,MDAMB-436细胞较MDA-MB-231细胞的DNA损伤严重及细胞凋亡率增加,两者比较差异均有统计学意义(P均<0.05)。两个细胞株8 Gy照射剂量的细胞焦点增长数及细胞凋亡增长率与10 Gy照射剂量比较,差异均无统计学意义(P均>0.05)。结论随着X射线照射剂量由0 Gy至10 Gy不断增强,乳腺癌细胞损伤不断增加,BRCA基因突变的乳腺癌细胞DNA损伤及细胞凋亡率均较BRCA基因非突变的乳腺癌细胞明显增加,具有更高的放射敏感性。更多还原

【Abstract】 Objective To investigate the effects of different ionizing radiation doses on DNA damage and apoptosis of breast cancer cell lines with and without BRCA mutations. Methods BRCA mutant cells(MDA-MB-436)and non-BRCA mutant cells(MDA-MB-231) were subjected to different doses of ionizing radiation:0,2,4,6,8,or 10 Gy. The percentage of apoptotic cells was assessed by flow cytometry. After 30 min of irradiation,DNA damage was detected using an immunofluorescence-based γH2AX focus assay.Results Increasing radiation dose was associated with greater double-strand DNA damage and apoptosis in both MDA-MB-436 and MDA-MB-231 cells,with the greatest effects reached at 8 Gy. At individual doses,DNA damage and apoptosis were significantly more severe in MDA-MB-436 cells than in MDA-MB-231 cells(P<0.05). Conclusions Double-strand DNA damage and apoptosis vary in proportion to radiation dose,and cells containing BRCA mutations may be more radiation-sensitive than cells lacking such mutations.更多还原