Identification and Validation of Candidate Radiation-responsive Genes for Human Biodosimetry

The aim of the present study is to analyze the global research trend of radiation-responsive genes and identify the highly reproducible radiation-responsive genes. Bibliometric methods were applied to analyze the global research trend of radiation-responsive genes. We found 79 publications on radiation-responsive genes from 2000 to 2017. A total of 35 highly reproducible radiation-responsive genes were identified. Most genes are involved in response to DNA damage, cell proliferation, cell cycle regulation, and DNA repair.The p53 signal pathway was the top enriched pathway. The expression levels of 18 genes in human B lymphoblastoid cell line（AHH-1） cells were significantly up-regulated in a dose-dependent manner at 24 h after exposure to 0-5 Gy ^60 Coγ-ray irradiation. Our results indicate that developing a gene expression panel with the 35 high reproducibility radiation-responsive genes may be necessary for qualitative and quantitative assessment after exposure.

射线联合嵌合启动子介导的自杀基因对肿瘤细胞的靶向杀伤作用

目的探讨放射线联合新型嵌合启动子介导辣根过氧化物酶／吲哚乙酸（HRP／IAA）自杀基因系统特异高效的抗肿瘤作用。方法构建含有4个串联放射反应元件CArG、含或不含巨细胞病毒（CMV）启动子的人端粒酶逆转录酶嵌合启动子，筛选肿瘤特异性及放射诱导性强的嵌合启动子，下游连接自杀基因辣根过氧化物酶（HRP），检测放射线联合基因治疗对肿瘤细胞HeLa、A549和MHCC97增殖及凋亡的影响。结果人胚肺成纤维细胞MRC-5中C4-hTC嵌合启动子的活性（0．1±0．0）明显低于肿瘤细胞株HeLa、A549和MHCC97（0．6±0．0、1．1±0．1和1．0±0．1，P〈0．01），经过6Gy射线诱导后，这种差异更加显著（活性分别为0．2±0．1、1．7±0．2、2．3±0．2和2．3±0．1，P〈0．01）。在肿瘤细胞株HeLa、A549和MHCC97中，嵌合启动子C4-hTC-HRP携带的自杀基因系统SER值分别为2．64、2．75和2．82，显著高于单纯hTERT启动子。在肿瘤细胞中，除阴性对照质粒pGL3-contr01．Luc外，自杀基因与放射治疗相联合对肿瘤细胞的生长抑制明显高于单一治疗方法，而联合组中pC4-hTC．HRP／IAA系统与放射联合的生长抑制作用最显著，对HeLa、A549和MHCC97细胞的生长抑制率分别为67．3％、69．0％和64．6％。在肿瘤细胞中，除阴性对照质粒pGL3-control-Luc外，联合组诱导的早期凋亡率明显高于单一治疗方法组，其中pC4-hTC-HRP／IAA系统与放射联合诱导的凋亡率最高，HeLa、A549和MHCC97细胞凋亡率分别为39．6％、33．0％和33．2％。结论新型嵌合启动子C4-hTC具有良好的肿瘤特异性及放射诱导性，放射线联合基因治疗对肿瘤细胞具有特异高效的杀伤作用，在肿瘤的基因放疗中具有较强的应用潜力。