Uniformed Services University, Armed Forces Radiobiology Research Institute, Scientific Research Department, Bethesda, Maryland 20889-5603, USA.
Int J Radiat Biol. 2009;85(10):837-50.
The aim was to evaluate the utility of multiple blood-protein biomarkers for early-response assessment of radiation exposure using a murine radiation model system.
BALB/c male mice (8-10 weeks old) were exposed to whole-body 60Co gamma-rays (10 cGy min(-1)) over a broad dose range (0-7 Gy). Blood protein biomarkers (i.e., Growth Arrest and DNA Damage Inducible Gene 45 or GADD45alpha, interleukin 6 or IL-6, and serum amyloid A or SAA) were measured by enzyme linked immunosorbent assay (ELISA) at 4, 24, 48, and 72 h after total-body irradiation (TBI).
Time- and dose-dependent increases in the protein targets were observed. The use of multiple protein targets was evaluated using multiple linear regression analysis to provide dose-response calibration curves for dose assessment. Multivariate discriminant analysis demonstrated enhanced dose-dependent separation of irradiated animals from control as the number of biomarkers increased.
Results from this study represent a proof-of-concept for multiple blood-proteins biodosimetry approach. It was demonstrated for the first time that protein expression profile could be developed not only to assess radiation exposure in male BALB/c mice but also to distinguish the level of radiation exposure, ranging from 1-7 Gy.
本研究旨在利用小鼠辐射模型系统，评估多种血液蛋白生物标志物在辐射暴露早期反应评估中的应用。
BALB/c 雄性小鼠（8-10 周龄）接受全身 60Coγ射线照射（10 cGy min(-1))，剂量范围较宽（0-7 Gy）。在全身照射（TBI）后 4、24、48 和 72 小时，通过酶联免疫吸附试验（ELISA）测量血液蛋白生物标志物（即生长停滞和 DNA 损伤诱导基因 45 或 GADD45alpha、白细胞介素 6 或 IL-6 和血清淀粉样蛋白 A 或 SAA）。
观察到蛋白靶标随时间和剂量呈依赖性增加。使用多元线性回归分析评估了多个蛋白靶标，以提供剂量评估的剂量反应校准曲线。多元判别分析表明，随着生物标志物数量的增加，照射动物与对照动物的剂量依赖性分离得到增强。
本研究结果代表了多血液蛋白生物剂量测定方法的概念验证。首次证明，不仅可以开发蛋白表达谱来评估雄性 BALB/c 小鼠的辐射暴露，而且可以区分 1-7 Gy 的辐射暴露水平。
