125I籽源持续低剂量率照射诱导人肺癌细胞的旁效应

观察125I籽源持续低剂量率照射诱导人肺癌细胞损伤的旁效应.选择对高剂量率外照射敏感性不同的A549人肺腺癌细胞和NCI-H446人小细胞肺癌细胞,采用125I籽源离体照射细胞模式,将直接受照细胞与未受照细胞共培养24h,应用CB微核法和γH2AX荧光免疫分析法,检测2Gy和4Gy125I籽源持续低剂量率照射诱导人肺癌细胞的微核形成和DNA双链断裂水平.结果表明,125I籽源照射能显著诱导A549和NCI-H446细胞的微核形成率和γH2AX位点形成率增加的旁效应,显示增强对肿瘤细胞的杀伤作用.旁效应强弱与累积照射剂量、肿瘤细胞的辐射敏感性相关:对高剂量率外照射敏感的NCI-H446细胞对低剂量率照射及其旁效应的敏感性高于A549细胞,但与直接辐射效应相比,125I籽源照射诱导A549细胞旁效应高于NCI-H446细胞,这两种细胞的辐射旁效应均随累积照射剂量增加而降低,提示介导旁效应的信号因子水平可能随细胞损伤程度的增加而下降.

Bystander effects of exposure to low-dose-rate 125I seeds on human lung cancers cells in vitro

The bystander effects induced by continuous low-dose-rate(LDR) ~(125)I seeds radiation on damage of human lung cancer cells were investigated.Human adenocarcinoma cell line AS49 and human small cell lung cancer cell line NCI-H446,which have different sensitivities to high-dose rate(HDR) external irradiation,were exposed di- rectly to ~(125)I seeds in vitro and co-cultured with unirradiated cells for 24 h.Using cytokinesis-blocking micronucleus method and T H2AX fluorescence immunoassay,bystander effects induced by 2Gy and 4Gy ~(125)I seed irradiation on micronucleus formation and DNA double-strand breaks (DSBs) of human lung cancer cells were detected and evalu- ated.The results showed that irradiation with t25I seeds can induce medium-mediated bystander effects in A.549 cells and NCI-H446 cells,exhibiting that both micronuclei formation and 7 H2AX focus formation in bystander cells were increased significantly compared with non-irradiated cells.The extent of DNA damage induced by bystander effects was correlated with accumulated radiation dose and radiosensitive of tumor cells.NCI-H446 cells that were sensitive to HDR 7 irradiation were more sensitive to continuous LDR irradiation and bystander effects than AS49.However,a comparison between the bystander effects and direct effects elicits the intensity of bystander responses of A549 cells was higher than that of NCI-H446 cells.A dose-related reduction in bystander responses was observed both in A549 cells and NCI-H446 cells,suggesting that the signaling factors involved in the bystander signaling pathways may de- crease with the increase of cell damages.