In vivo formation and repair of DNA double-strand breaks after computed tomography examinations

被引:356
作者
Löbrich, M
Rief, N
Kühne, M
Heckmann, M
Fleckenstein, J
Rübe, C
Uder, M
机构
[1] Univ Saarland, Fachrichtung Biophys, D-66421 Homburg, Germany
[2] Univ Saarland, Klin Diagnost & Intervent Radiol, D-66421 Homburg, Germany
[3] Univ Saarland, Klin Strahlentherapie & Radioonkol, D-66421 Homburg, Germany
[4] Univ Erlangen Nurnberg, Inst Diagnost Radiol, D-91054 Erlangen, Germany
关键词
gamma-H2AX foci; ionizing radiation; low radiation doses; radiosensitivity; blood lymphocytes;
D O I
10.1073/pnas.0501895102
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:8984 / 8989
页数:6
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