Normal expression of DNA repair proteins, hMre11, Rad50 and Rad51 but protracted formation of Rad50 containing foci in X-irradiated skin fibroblasts from radiosensitive cancer patients.
Normal expression of DNA repair proteins, hMre11, Rad50 and Rad51 but protracted formation of Rad50 containing foci in X-irradiated skin fibroblasts from radiosensitive cancer patients.
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DOI：
10.1038/sj.bjc.6601878
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发表时间：
2004-06-14
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
约5%接受放射治疗的肿瘤患者出现急性或晚期放射毒性作用，其分子机制尚不清楚。在这项研究中，我们评估了DNA修复蛋白在癌症患者放射治疗超敏反应中的潜在作用。应用Western blot和局灶免疫荧光技术分别研究了肿瘤早期放疗不良反应患者皮肤成纤维细胞株中DNA修复蛋白hMre11、Rad50和Rad51的表达水平和局灶核分布。来自对放射治疗反应正常的癌症患者的细胞以及来自表面健康受试者的细胞作为对照。体外辐照后的细胞放射敏感性通过克隆生存试验进行评估。克隆生存试验和DNA修复蛋白的Western blot分析未发现体外细胞放射敏感性和来自放射治疗过敏反应的癌症患者的成纤维细胞的蛋白质表达水平或迁移模式有任何异常。相比之下，来自放射敏感患者的体外辐照细胞显示出局灶集中Rad50蛋白的细胞核数量明显高于两个对照组。观察到放射治疗急性副反应的癌症患者细胞中放射诱导的Rad50病灶分布的改变可能有助于其放射治疗结果。这些数据表明Rad50病灶分析对于预测癌症患者对放疗的临床反应是有用的。
About 5% of oncology patients treated by radiation therapy develop acute or late radiotoxic effects whose molecular mechanisms remain poorly understood. In this study, we evaluated the potential role of DNA repair proteins in the hypersensitivity of cancer patients to radiation therapy. The expression levels and focal nuclear distribution of DNA repair proteins, hMre11, Rad50 and Rad51 were investigated in skin fibroblasts strains derived from cancer patients with adverse early skin reaction to radiotherapy using Western blot and foci immunofluorescence techniques, respectively. Cells from cancer patients with normal reaction to radiotherapy as well as cells from apparently healthy subjects served as controls. Cellular radiosensitivity after in vitro irradiation was assessed by the clonogenic survival assay. The clonogenic survival assay and Western blot analysis of the DNA repair proteins did not reveal any abnormalities in cellular radiosensitivity in vitro and in protein expression levels or their migration patterns in the fibroblasts derived from cancer patients with hypersensitive reaction to radiotherapy. In contrast, in vitro irradiated cells from radiosensitive patients exhibited a significantly higher number of nuclei with focally concentrated Rad50 protein than in both control groups. The observed alteration of the distribution of radiation-induced Rad50 foci in cells derived from cancer patients with acute side reactions to radiotherapy might contribute to their radiation therapy outcome. These data suggest the usefulness of the Rad50 foci analysis for predicting clinical response of cancer patients to radiotherapy.
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影响因子：
4.8
作者：
Kitahara, O;Katagiri, T;Nakamura, Y
通讯作者：
Nakamura, Y
DOI：
10.1016/s0360-3016(99)00108-x
发表时间：
1999-07-15
影响因子：
7
作者：
Oppitz, U;Bernthaler, U;Flentje, M
通讯作者：
Flentje, M
DOI：
10.1016/s0027-5107(03)00009-5
发表时间：
2003-04-09
影响因子：
2.3
作者：
Yuan, SSF;Chang, HL;Lee, EYHP
通讯作者：
Lee, EYHP
影响因子：
8.8
作者：
Appleby JM;Barber JB;Levine E;Varley JM;Taylor AM;Stankovic T;Heighway J;Warren C;Scott D
通讯作者：
Scott D
DOI：
10.1073/pnas.96.13.7376
发表时间：
1999-06-22
影响因子：
11.1
作者：
Luo, GB;Yao, MS;Petrini, JHJ
通讯作者：
Petrini, JHJ