CAJ | 학술논문

目的了解不同组织来源癌细胞株和人体肿瘤组织原代细胞的DNA双链断裂损伤修复的个体差异性,探寻预测癌细胞辐射敏感性的生物指标.方法 60Coγ射线照射诱发DNA损伤,脉冲电场凝胶电泳检测DNA双链断裂损伤修复,细胞克隆形成能力法检测细胞辐射敏感性.结果 8个不同组织来源癌细胞株的辐射敏感性有较大的差异(D0为0.65～2.15 Gy),不同细胞株20 Gyγ射线照射诱发产生的DNA双链断裂原初损伤有一定的差别,但与细胞辐射抗性无相关性.辐射敏感细胞SX-10的DNA双链断裂修复缺陷发生在早期快速修复相,而A2780细胞的修复缺陷是发生在晚期慢速修复相.20 Gy照射修复2 h后DNA双链断裂残留量与细胞辐射敏感性指标D0或SF2值有显著的相关性.不同个体患者脑肿瘤组织原代细胞之间,辐射诱发DNA双链断裂的修复反应存在明显差异,修复2 h后残留损伤的个体差异性分布类似于癌细胞株.结论 DNA双链断裂残留损伤与癌细胞辐射抗性有显著相关性,可作生物指标预测肿瘤组织细胞对放射治疗的反应性.
목적 료해불동조직래원암세포주화인체종류조직원대세포적DNA쌍련단렬손상수복적개체차이성,탐심예측암세포복사민감성적생물지표.방법 60Coγ사선조사유발DNA손상,맥충전장응효전영검측DNA쌍련단렬손상수복,세포극륭형성능역법검측세포복사민감성.결과 8개불동조직래원암세포주적복사민감성유교대적차이(D0위0.65～2.15 Gy),불동세포주20 Gyγ사선조사유발산생적DNA쌍련단렬원초손상유일정적차별,단여세포복사항성무상관성.복사민감세포SX-10적DNA쌍련단렬수복결함발생재조기쾌속수복상,이A2780세포적수복결함시발생재만기만속수복상.20 Gy조사수복2 h후DNA쌍련단렬잔류량여세포복사민감성지표D0혹SF2치유현저적상관성.불동개체환자뇌종류조직원대세포지간,복사유발DNA쌍련단렬적수복반응존재명현차이,수복2 h후잔류손상적개체차이성분포유사우암세포주.결론 DNA쌍련단렬잔류손상여암세포복사항성유현저상관성,가작생물지표예측종류조직세포대방사치료적반응성.
Objective To understand the variation of the DNA double-strand break rejoining capacity among different cultured cancer cell lines and the primary cancer cells from brain cancer patients,and to explore the predictor of radiotherapy responses of cancers. Methods DNA double-strand breaks (DSBs) were induced by 60Co γ-irradiation. Pulsed-field gel electrophoresis was used to analyze the initial production and rejoining of DNA DSBs. Radiosensitivity was determined by in vitro assay of clonogenic-forming capacity. Results A wide variation of radiosensitivity, e.g. The survival parameter of D0 varied from 0.65 to 2.15 Gy, was displayed among the eight cell lines derived from different type of cancers. Although differential level of initial DNA DSBs induced by 20 Gy γ-rays was observed among various cell lines, it was not correlated with the radiosensitivity. The deficiency of DNA DSB rejoining in radiosensitive cell lines was shown either in the early rapid-rejoining phase (SX-10 cells) or in the late slow-rejoining phase (A2780 cells). A significant relationship was observed between the residual level of DNA DSBs measured at 2 h post-20 Gy irradiation and the cellular radioseusitivity (D0 or SF2). The kinetic curves of rejoining DNA DSBs in the primary human brain tumor cells indicated a variation on DSB rejoining capacity among different individual tumor. The residual level of DNA DSBs after 2 h of rejoining post 20 Gy irradiation in primary human brain tumor cells is compatible to the results obtained in vitro culture cancer cell lines. Conclusions The residual level of DNA DSBs is correlated with radioresistance of cancer cells, and the residual DNA damage is a useful parameter in predicting the response of tumor tissue to radiotherapy.