60Co γ射线照射正常人外周血基因组合表达模型的建立

Establishment of a biodosimeter model based on multiple gene expressions in human peripheral blood cells after 60Co γ-rays irradiation

目的 探讨基因组合表达模型作为辐射生物剂量计的可行性。方法 0~8 Gy 60Co γ射线照射正常人外周血，利用实时荧光定量PCR检测10个辐射敏感基因表达变化，应用逐步回归方法建立基因组合表达模型；双盲法验证模型估算剂量的准确性。结果 照后6和12 h，10个辐射敏感基因的表达水平随受照剂量的增加而增加，均呈现良好的剂量-效应关系（R2=0.61~0.97，P〈 0.05）；TNFSF4、PHPT1和FDXR基因相对表达量存在较大的个体间差异；照后6 h，PCNA、CCNG1、TNFSF4、PHPT1、GADD45A和FDXR建立的基因组合表达模型R2为0.88（F=54.8，P〈0.001）；照后12 h，PCNA、CCNG1、TNFSF4、MDM2、GDF15和TNFRSF10B建立的基因组合表达模型R2为0.82（F=42.767，P〈0.001）；各时间点基因组合表达模型估算的受照剂量均接近于真实照射剂量。结论 基因组合表达模型具备作为辐射生物剂量计的基本条件。

Objective To investigate a potential radiation biodosimetry based on multiple gene expressions. Methods Human peripheral blood were exposed to 60Co γ-rays at doses from 0 to 8 Gy. The mRNA expression levels of 10 selected genes were detected 6 and 12 h after irradiation by RT-PCR. Individual variation was also examined. An optimal mathematical model of the dose response of these gene expression levels at each time point was obtained by the stepwise regression method. A blind test was conducted to validate the statistical accuracy of dose estimation. Results The 10 selected genes expression levels at each time point were significantly increased along with dose from 0.5 to 8 Gy （R2=0.61-0.97, P〈0.05）. Individual variations were evident in the gene expressions of TNFSF4, PHPT1 and FDXR. The gene expression levels of PCNA, CCNG1, TNFSF4, PHPT1, GADD45A and FDXR were incorporated into the model at 6 h after exposure （R2=0.88, F=54.8, P〈0.001）; the gene expression levels of PCNA, CCNG1, TNFSF4, MDM2, GDF15 and TNFRSF10B were included in the model at 12 h after irradiation （R2=0.82, F=42.767, P〈0.001）. These two statistical models can be utilized for the dose estimation accurately. Conclusions The multiple gene expressions have a potential as a radiation biodosimetry.