Bürger Susann, Schindler Detlev, Fehn Martin, Mühl Bettina, Mahrhofer Hartmut, Flentje Michael, Hoehn Holger, Seemanová Eva, Djuzenova Cholpon S
Klinik für Strahlentherapie der Universität Würzburg, Würzburg, Germany.
Environ Mol Mutagen. 2006 May;47(4):260-70. doi: 10.1002/em.20202.
Nijmegen breakage syndrome (NBS) patients and carriers are predisposed to malignancy and are often treated with X-irradiation. In the present study, the single-cell gel electrophoresis (Comet) assay was used to examine radiation-induced DNA damage and repair in peripheral blood mononuclear cells from NBS patients (n=13) and carriers (n=36) of six unrelated families. Cells from apparently healthy donors (n=10) and from breast cancer patients with normal clinical radiosensitivity (n=10) served as controls. Cells were irradiated with 5 Gy of X-rays and assayed for initial DNA damage and for residual DNA damage after 40 min of repair; the kinetics of DNA repair also was estimated. In addition, the nuclear area of unirradiated cells was extracted from the Comet data. The initial radiation-induced DNA fragmentation indicated that cells from members of two out of six NBS families were significantly more sensitive to X-irradiation than cells from the controls. Cells from four NBS families had longer DNA repair half-time values, while cells from five NBS families had significantly increased residual DNA damage following repair. The mean nuclear area of unirradiated cells processed in the Comet assay was 1.3-fold higher in cells from all NBS families than in the controls (P<0.05). Notably, the Comet assay parameters (initial and residual DNA damage and the repair kinetics) of irradiated NBS cells predicted the carrier status of the majority (86%) of blindly tested individuals. The prediction of NBS status was higher if the nuclear area of unirradiated cells was used as the endpoint. The results of this study suggest that the impaired radiation response of NBS cells should be taken into account if radiotherapy of NBS patients and carriers is required.
尼美根断裂综合征（NBS）患者及携带者易患恶性肿瘤，且常接受X射线照射治疗。在本研究中，采用单细胞凝胶电泳（彗星）试验检测了6个无关家族的NBS患者（n = 13）及携带者（n = 36）外周血单个核细胞中辐射诱导的DNA损伤及修复情况。来自表面健康的供者（n = 10）及临床放射敏感性正常的乳腺癌患者（n = 10）的细胞作为对照。细胞接受5 Gy的X射线照射，并检测初始DNA损伤及修复40分钟后的残留DNA损伤；同时还评估了DNA修复动力学。此外，从彗星试验数据中提取未照射细胞的核面积。初始辐射诱导的DNA片段化表明，6个NBS家族中有2个家族成员的细胞对X射线照射的敏感性显著高于对照细胞。4个NBS家族的细胞DNA修复半衰期值更长，而5个NBS家族的细胞在修复后残留DNA损伤显著增加。在彗星试验中处理的未照射细胞的平均核面积，在所有NBS家族的细胞中比对照细胞高1.3倍（P<0.05）。值得注意的是，照射后NBS细胞的彗星试验参数（初始和残留DNA损伤及修复动力学）预测了大多数（86%）盲目检测个体的携带者状态。如果将未照射细胞的核面积作为终点指标，对NBS状态的预测会更高。本研究结果表明，如果需要对NBS患者及携带者进行放射治疗，应考虑NBS细胞受损的辐射反应。
