不同癌细胞株放射敏感性与端粒长度的关系

目的:研究人类不同癌细胞株放射敏感性与端粒长度的关系,寻求放射敏感性预测的可行指标。方法:以不同层次的人类癌细胞株为实验对象,既包括鳞癌(Hep-2)、腺癌(ZR-75-30、MCF-7、MDA-MB-435S、T-47-D、F539-1590)、胶质瘤U251,又含有同一病理类型的不同亚株(5种不同的乳腺癌细胞株),还包括辐射诱导建立的放射抗拒细胞株(Hep-2R),用克隆形成实验拟合细胞存活曲线测定8株细胞的放射生物学参数,Southernblotting法测量各细胞株的端粒限制片断长度(TRF),分析放射敏感性与端粒限制片断长度的关系。结果:8株细胞的放射敏感性各不相同,Hep-2(人喉鳞癌细胞株)的SF2=0.4148,U251(人恶性胶质瘤细胞株)的SF2=0.7520,腺癌细胞株介于二者之间;端粒长度在放射抗拒细胞株Hep-2R中达11.12kb,数倍长于鳞癌亲本株或腺癌细胞株。端粒长度与放射敏感性参数SF2(r=0.786,P<0.05)、D0(r=0.905,P<0.01)均成正相关关系。结论:端粒长度与人癌细胞株的放射敏感性描述参数SF2、D0成正相关关系,故端粒长度与人癌细胞株的放射敏感性成负相关关系,它可以作为放射敏感性预测指标之一。

Relationship between Radiosensitivity and Telomere Length in Human Carcinoma Cell Lines

Objective: To investigate the relationship between radiosensitivity and telomere length among different human carcinoma cell lines, and to search for a valid predictor of radiosensitivity. Methods: Eight human carcinoma cell lines were used, including five human breast cancer cell lines(ZR-75-30, MCF-7, MDA-MB-435S, T-47-D and F539-1590), two human larynx squamous carcinoma cell lines(Hep-2 and Hep-2R) and a human malignant glioma cell line U251. Among them, especially, the radioresistant cell line Hep-2R was established and isolated from a radiosensitive human larynx squamous carcinoma cell line Hep-2 by our center. The radiobiology characteristics of the eight lines were analyzed by the method of colony-forming assay. Radiosensitivity parameters were calculated. Telomere length(mean length of telomere restriction fragments, TRF) was examined by the method of southern blotting graphy analysis. Results: The radioresistance of Hep-2R cell line was stable not only in long-term subculturing but also in frozen samples. Radiosensitivity parameters were different among those lines. The SF_2 values of Hep-2 and U251 were 0.414 8 and 0.752 0 respectively, the SF_2 values of breast cell lines were between those of Hep-2 and U251. The TRF of Hep-2R was 11.12 kb, longer than three times of its parental line. There was a positive correlation between SF_2 and TRF(r=0.786, P<0.05), so was it between D_0 and TRF(r=0.905, P<0.01). Conclusion: It is concluded that radiosensitivity and telomere length(TRF) are negatively correlated, and TRF could be a valid predictor for radiosensitivity.