Strasser Hans, Grabenbauer Gerhard G, Sprung Carl N, Sauer Rolf, Distel Luitpold V R
Department of Radiation Oncology, Friedrich Alexander University of Erlangen-Nuremberg, Erlangen, Germany.
Strahlenther Onkol. 2007 Aug;183(8):447-53. doi: 10.1007/s00066-007-1683-4.
DNA double-strand breaks (dsbs) in lymphoblastoid cell lines (LCLs), fibroblasts and white blood cells from healthy donors, cancer patients with and without late effects of grade 3-4 (RTOG) as well as donors with known radiosensitivity syndromes were examined with the aim to detect dsb repair ability as a marker for radiosensitivity.
LCLs from six healthy donors, seven patients with a heterozygous or homozygous genotype for ataxia-telangiectasia (ATM) and Nijmegen breakage syndrome (NBS), two patients with a late toxicity of grade 3-4 (RTOG), and one cell line with a ligase IV-/- status and its parental cell line were examined. Furthermore, fibroblasts from patients with ATM, NBS, two healthy control individuals, and leukocytes from 16 healthy and 22 cancer patients including seven patients with clinical hypersensitivity grade 3 (RTOG) were examined. Cells were irradiated in vitro with 0-150 Gy. Initial damage as well as remaining damage after 8 and 24 h were measured using constant field gel electrophoresis.
In contrast to cells derived from patients homozygous for NBS, impaired dsb repair ability could be detected both in fibroblast and lymphoblastoid cells from ATM and ligase IV-/- patients. The dsb repair ability of all 38 leukocyte cell lines (patients with grade 3-4 late effects and controls) was similar, whereas the initial damage among healthy donors was less.
Despite showing a clinically elevated radiosensitivity after irradiation, the DNA repair of the patients with clinical hypersensitivity grade 3 (RTOG) appeared to be normal. Other mechanisms such as mutations, altered cell cycle or defective apoptosis could play a critical role toward determining radiosensitivity.
检测来自健康供者、有或无3 - 4级晚期效应（放射肿瘤学协作组标准）的癌症患者以及已知有放射敏感性综合征的供者的淋巴母细胞系（LCL）、成纤维细胞和白细胞中的DNA双链断裂（dsb），以检测dsb修复能力作为放射敏感性的标志物。
检测了来自6名健康供者、7名共济失调毛细血管扩张症（ATM）和尼曼匹克氏症（NBS）杂合或纯合基因型患者、2名有3 - 4级晚期毒性（放射肿瘤学协作组标准）的患者的LCL，以及1个连接酶IV基因敲除状态的细胞系及其亲本细胞系。此外，还检测了患有ATM、NBS的患者的成纤维细胞、2名健康对照个体，以及16名健康和22名癌症患者的白细胞，其中包括7名临床超敏反应3级（放射肿瘤学协作组标准）的患者。细胞在体外接受0 - 150 Gy的照射。使用恒定电场凝胶电泳测量初始损伤以及照射8小时和24小时后的残留损伤。
与NBS纯合患者来源的细胞不同，在ATM患者和成纤维细胞以及连接酶IV基因敲除患者的淋巴母细胞系中均检测到dsb修复能力受损。所有38个白细胞细胞系（有3 - 4级晚期效应的患者和对照）的dsb修复能力相似，而健康供者中的初始损伤较少。
尽管临床超敏反应3级（放射肿瘤学协作组标准）的患者在照射后表现出临床上较高的放射敏感性，但其DNA修复似乎正常。其他机制，如突变、细胞周期改变或凋亡缺陷，可能在决定放射敏感性方面起关键作用。
