In vivo formation and repair of DNA double-strand breaks after computed tomography examinations
In vivo formation and repair of DNA double-strand breaks after computed tomography examinations
复制标题
DOI：
10.1073/pnas.0501895102
复制
发表时间：
2005-06-21
影响因子：
11.1
通讯作者：
Uder, M
中科院分区：
文献类型：
--
作者：
Löbrich, M;Rief, N;Uder, M
电离辐射可对人体造成各种有害影响，最重要的是诱发癌症。DNA双链断裂（DSB）是电离辐射引起的最重要的遗传损伤之一，可引发致癌作用。我们已经列举了γ-H2 AX病灶作为从个人接受胸部和/或腹部计算机断层扫描检查的淋巴细胞中DSB的措施。由计算机断层扫描检查引起的DSB的数量被发现线性依赖于剂量长度产品，放射诊断单位，这是成比例的局部剂量和暴露的身体的长度。对辐射后1天内淋巴细胞取样的分析提供了与DSB修复相关的γ-H2 AX病灶体内丢失的动力学。有趣的是，与体外获得的结果相反，正常个体将DSB修复到背景水平。一名先前在放疗后表现出严重副作用的患者在放疗后的不同采样时间显示出比正常个体高数倍的γ-H2 AX病灶水平。从该患者获得的成纤维细胞的γ-H2 AX和脉冲场凝胶电泳分析证实了实质性的DSB修复缺陷。此外，这些成纤维细胞显示出显着的体外放射敏感性。这些数据表明，DSB的体内诱导和修复可以在暴露于低辐射剂量的个体中进行评估，为DSB修复研究增加了进一步的维度，并提供了在诊断辐射程序后识别修复受损个体的机会。
Ionizing radiation can lead to a variety of deleterious effects in humans, most importantly to the induction of cancer. DNA double-strand breaks (DSBs) are among the most significant genetic lesions introduced by ionizing radiation that can initiate carcinogenesis. We have enumerated gamma-H2AX foci as a measure for DSBs in lymphocytes from individuals undergoing computed tomography examination of the thorax and/or the abdomen. The number of DSBs induced by computed tomography examination was found to depend linearly on the dose-length product, a radiodiagnostic unit that is proportional to both the local dose delivered and the length of the body exposed. Analysis of lymphocytes sampled up to 1 day postirradiation provided kinetics for the in vivo loss of gamma-H2AX foci that correlated with DSB repair. Interestingly, in contrast to results obtained in vitro, normal individuals repair DSBs to background levels. A patient who had previously shown severe side effects after radiotherapy displayed levels of gamma-H2AX foci at various sampling times postirradiation that were several times higher than those of normal individuals. gamma-H2AX and pulsed-field gel electrophoresis analysis of fibroblasts obtained from this patient confirmed a substantial DSB repair defect. Additionally, these fibroblasts showed significant in vitro radiosensitivity. These data show that the in vivo induction and repair of DSBs can be assessed in individuals exposed to low radiation doses, adding a further dimension to DSB repair studies and providing the opportunity to identify repair-compromised individuals after diagnostic irradiation procedures.