Indicators of late normal tissue response after radiotherapy for head and neck cancer:: fibroblasts, lymphocytes, genetics, DNA repair, and chromosome aberrations
Indicators of late normal tissue response after radiotherapy for head and neck cancer:: fibroblasts, lymphocytes, genetics, DNA repair, and chromosome aberrations
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DOI：
10.1016/s0167-8140(02)00167-6
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发表时间：
2002-08-01
影响因子：
5.7
通讯作者：
Dahm-Daphi, J
中科院分区：
文献类型：
--
作者：
Borgmann, K;Röper, B;Dahm-Daphi, J
目的：研究放疗后晚期组织反应、细胞敏感性和真皮成纤维细胞DNA修复能力以及淋巴细胞染色体畸变之间的关系。这项研究是特别设计来比较细胞参数的患者最大的差异，在后期组织reactions.Materials和方法：这项研究是与16对配对的头部和颈部癌症患者2-7年后，治疗性治疗表现出最大的差异（I级与3级），在后期正常组织反应。临床终点为纤维化、毛细血管扩张。使用放射治疗肿瘤组评分的粘膜炎和口干。通过聚合酶链反应-单链构象多态性和测序分析，检测3级反应患者共济失调毛细血管扩张症（AT）、奈梅亨断裂综合征（NBS）、MRE 11、RAD 50和DNA连接酶IV基因的突变。使用从活检中获得的皮肤成纤维细胞，通过集落形成以及使用恒场凝胶电泳诱导和修复DNA双链断裂（dsb）来确定细胞敏感性。淋巴细胞被用来测量染色体损伤，无论是在中期使用常规染色体分析或在去使用过早染色体凝聚（PCC）technique.Results：极端晚期反应（3级）的患者没有表现出AT，NBS，MRE 11或RAD 50突变的证据。对成纤维细胞的研究表明，极端的晚期反应既不与明显的细胞辐射敏感性相关，也不与dsb修复能力的差异相关。相反。在淋巴细胞中测量的染色体损伤存在显著差异。在体外接受6戈伊照射后，从过度反应患者中提取的淋巴细胞平均显示出比从轻度反应患者中分离的淋巴细胞显著更高的致死畸变数量（7.2+/-0.8 vs. 5.0+/-0.3）。PCC fragments.Conclusion：这项研究表明，淋巴细胞比成纤维细胞更有前途的预测患者放疗后的正常组织反应。(C)2002爱思唯尔科学爱尔兰有限公司保留所有权利。
Purpose: To investigate the relationship between late tissue response after radiotherapy, cellular sensitivity and DNA repair capacity measured in dermal fibroblasts and chromosomal aberrations measured in lymphocytes. The study was in particular designed to compare cellular parameters of patients with maximum differences in late tissue reactions.Materials and methods: The study was performed with 16 pair-wise matched head and neck cancer patients 2-7 years after curative therapy exhibiting maximum differences (grade I vs. grade 3) in late normal tissue reactions. Clinical endpoints were fibrosis, telangiectasia. mucositis and xerostomia using the radiation therapy oncology group score. Patients with grade 3 reactions were tested for mutations in ataxia telangiectasia (AT), Nijmegen Breakage Syndrome (NBS), MRE11, RAD50 and DNA ligase IV genes by means of polymerase chain reaction-single-strand conformation polymorphism and sequencing analysis. Skin fibroblasts obtained from biopsies were used to determine the cellular sensitivity by colony formation and the induction and repair of DNA double-strand breaks (dsb) using constant-field gel electrophoresis. Lymphocytes were taken to measure chromosomal damage either in metaphase using conventional chromosome analysis or in Go using premature chromosome condensation (PCC)-technique.Results: Patients with extreme late reactions (grade 3) showed no evidence for an AT, NBS, MRE11 or RAD50 mutation. Studies with fibroblasts revealed that extreme late reactions were associated neither with a pronounced cellular radiosensitivity nor with a difference in dsb repair capacity. In contrast. there was a significant difference in chromosomal damage measured in lymphocytes. After in vitro irradiation with 6 Gy, lymphocytes taken from overreacting patients showed on average a significantly higher number of lethal aberrations than lymphocytes isolated from patients with mild reactions (7.2+/-0.8 vs. 5.0+/-0.3). Similar differences were found for PCC fragments.Conclusion: This study suggests that lymphocytes are more promising than fibroblasts to predict patient's normal tissue response after radiotherapy. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.