Relationship between clonogenic radiosensitivity, radiation-induced apoptosis and DNA damage/repair in human colon cancer cells.
Relationship between clonogenic radiosensitivity, radiation-induced apoptosis and DNA damage/repair in human colon cancer cells.
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DOI：
10.1038/sj.bjc.6601427
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发表时间：
2003-12-15
影响因子：
8.8
通讯作者：
Hirst, D G
中科院分区：
文献类型：
--
作者：
Dunne, A L;Price, M E;Mothersill, C;McKeown, S R;Robson, T;Hirst, D G
正常和肿瘤组织的固有辐射敏感性是放射治疗结果的主要决定因素。目前还没有一个既定的测试，可以用来常规测量细胞的放射敏感性在一个人的癌症的方式，可以告知治疗计划。本研究的目的是在四种人结直肠腺癌细胞系中评估作为辐射反应替代标志物的两个可能终点--细胞凋亡和DNA单链断裂的诱导--并将结果与传统克隆形成试验的结果进行比较。将已知放射敏感性不同的细胞系（SW 707、SW 480、SW 48和HT 29）暴露于范围为0.5至5戈伊的单剂量X射线，并使用克隆形成测定法测量细胞存活。在荧光显微镜下的形态学的基础上确定细胞凋亡，并使用碱性彗星试验的适应性测量DNA损伤/修复，作为尾矩。2戈伊剂量下的存活分数（SF 2）与相同剂量后24小时凋亡细胞百分比之间的关系很复杂，但细胞凋亡准确地预测了SF 2测量的放射敏感性顺序。使用碱性彗星试验2戈伊后测得的初始损伤与SF 2密切相关（r2=0.95），而初始DNA损伤修复率与SF 2之间没有相关性。
The intrinsic radiation sensitivity of normal and tumour tissue is a major determinant of the outcome of radiotherapy. There is currently no established test that can be used routinely to measure the radiosensitivity of the cells in an individual patient's cancer in a manner that can inform treatment planning. The purpose of this study was to evaluate, in four human colorectal adenocarcinoma cell lines, two possible end points as surrogate markers of radiation response – apoptosis and induction of DNA single-strand breaks – and to compare the results with those of a conventional clonogenic assay. Cell lines (SW707 SW480, SW48 and HT29) known to differ in radiosensitivity were exposed to single doses of X-rays ranging from 0.5 to 5 Gy and cell survival was measured using the clonogenic assay. Apoptosis was determined on the basis of morphology under fluorescent microscopy and DNA damage/repair was measured, as tail moment, using an adaptation of the alkaline comet assay. The relationship between surviving fraction at 2 Gy (SF2) and the percentage of apoptotic cells 24 h after the same dose was complex, but apoptosis accurately predicted the order of radiosensitivities as measured by SF2. Initial damage measured after 2 Gy using the alkaline comet assay gave a close correlation with SF2 (r2=0.95), whereas there was no correlation between initial DNA damage repair rate and SF2.