Leukocyte DNA damage after multi-detector row CT: A quantitative biomarker of low-level radiation exposure
Leukocyte DNA damage after multi-detector row CT: A quantitative biomarker of low-level radiation exposure
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DOI：
10.1148/radiol.2421060171
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发表时间：
2007-01-01
期刊：
影响因子：
19.7
通讯作者：
Goh, Vicky
中科院分区：
文献类型：
--
作者：
Rothkamm, Kai;Balroop, Sheena;Goh, Vicky
目的：为了前瞻性地确定γ H2AX是否（磷酸化形式的H2AX组蛋白变体）的可视化和外周血单核细胞（PBMC）中诱导的DNA损伤的定量可用于估计经历多探测器计算机断层扫描（CT）的成人患者所接受的辐射剂量。在获得机构审查委员会批准和患者知情同意书后，（平均年龄，63.8岁），将接受胸部-腹部-骨盆CT或胸部。仅招募CT。将扫描前获得的静脉血样品在体外暴露于不同的辐射剂量并孵育5 - 30分钟以获得γ H2AX聚焦产额的参考值。在CT后5 - 30分钟采集额外的血液样本。分离、固定白细胞，并针对γ H2AX表达进行染色。用荧光显微镜测定γ H2AX焦点产率，并通过比较CT后焦点产率与体外CT前焦点产率来估计CT期间递送的辐射剂量。这些CT辐射剂量进行了比较，通过使用体模剂量学和蒙特卡罗数据集计算的剂量。采用线性回归、离散指数检验和污染泊松法对数据进行分析。与CT前采集的血样中的γ H2AX病灶产率相比，（每个细胞0.06个病灶+/-0.01 [平均值+/-平均值误差]），胸腹盆CT扫描后5分钟采集的血样中的产率（每个细胞0.52个病灶+/-0.02）高8 - 10倍，对应于平均辐射剂量或16.4 mGy（95%置信区间：15.1，17.7）。1例患者胸部CT后的平均产额为0.24个病灶/细胞+/-0.04，相当于平均辐射闭合6.3 mGy +/-1.4。相比之下，体模剂量计算的总血液剂量为13.85 mGy与全身CT和5.16 mGy与胸部CT。结论：γ H2AX焦点产量在血细胞可能是一个有用的定量生物标志物的人体低水平辐射照射。
Purpose: To prospectively determine if gamma H2AX (phosphorylated form of H2AX histone variant)-based visualization and quantification of DNA damage induced in peripheral blood mononuclear cells (PBMCs) can be used to estimate the radiation dose received by adult patients who undergo multidetector computed tomography (CT).Materials and Methods: After institutional review board approval and written informed patient consent were obtained, eight women and five men (mean age, 63.8 years) who would be undergoing chest-abdominal-pelvic CT or chest. CT only were recruited. Venous blood samples obtained before scanning were exposed to different radiation doses in vitro and incubated for 5-30 minutes to obtain referenced values of gamma H2AX focus yield. Additional blood samples were taken 5-30 minutes after CT. Leukocytes were isolated, fixed, and stained for gamma H2AX expression. The gamma H2AX focus yields,were determined with fluorescence microscopy, and the radiation doses delivered during CT were estimated by comparing post-CT focus yields with in vitro pre-CT focus yields. These CT radiation doses were compared with doses calculated by using phantom dosimetry and Monte Carlo data sets. Data were analyzed by using linear regression, the dispersion index test, and the contaminated Poisson method.Results: Compared with the gamma H2AX focus yields in blood samples taken before CT (0.06 focus per cell +/- 0.01 [mean +/- error of mean]), the yields in blood samples taken 5 minutes after chest-abdominal-pelvic CT (0.52 focus per cell +/- 0.02) were 8-10-fold higher and corresponded to a mean radiation dose or 16.4 mGy (95% confidence interval: 15.1, 17.7). The mean yield of 0.24 focus per cell +/- 0.04 in one patient after chest CT corresponded to a mean radiation close of 6.3 mGy +/- 1.4. In comparison, phantom dosimetry-calculated total blood doses were 13.85 mGy with whole-body CT and 5.16 mGy with chest CT.Conclusion: gamma H2AX focus yield in blood cells may he a useful quantitative biomarker of human low-level radiation exposure.