Honkanen J, Rantanen V, Kulmala J, Grénman R, Klemi P, Pekkola K
Department of Gynecology and Obstetrics, University of Turku, Finland.
J Cancer Res Clin Oncol. 1998;124(8):415-20. doi: 10.1007/s004320050193.
The in vitro radiosensitivity of dermal fibroblasts has been found to vary between individuals, and a number of studies have also shown that this parameter correlates with radiation-induced late injuries in clinical radiotherapy. In addition, certain genetic disorders are known to effect radiosensitivity, e.g. normal tissues of patients homozygous or heterozygous for the ataxia teleangiectasia gene show unusual sensitivity to radiation both in vivo and in vitro. Thus, it has been assumed that there is a genetically determined component resulting in a certain intrinsic cellular radiation response in an individual. To study this possible relationship between different cells of a specific patient, we established eight pairs of dermal and tumor fibroblast cultures. The donor patients had either adenocarcinoma of the uterus or squamous cell carcinoma (SCC) of the head and neck. The radiosensitivity of these strains was determined by a 96-well plate clonogenic assay, previously used by us for radiosensitivity testing of cancer cells. From a paired comparison, the values for the cell fraction surviving 2.0 Gy (SF2), of both fibroblast strains, were found to be on the same level in five out of eight cases. In patient 6, the SF2 of tumor fibroblasts was significantly higher than that of dermal fibroblasts (P=0.0014). In two additional cases the tendency was the same, but not statistically significant. As groups, the two types of fibroblasts did not differ from each other, mean SF2 values of 0.24+/-0.07 and 0.21+/-0.05, respectively. The SF2 of tumor fibroblasts from SCC patients proved to be significantly higher than that of the adenocarcinoma patients (P=0.030). These preliminary results indicate that the in vitro radiosensitivity of tumor fibroblasts correlates with normal cell sensitivity in many cases, but not in all. The radiosensitivity of tumor fibroblasts also seems to follow the level of in vitro radiosensitivity determined for the corresponding histological type of tumor cells. Further studies are needed to determine more closely the relationship between the radiosensitivities of tumor cells and tumor fibroblasts, thus evaluating the possibility of testing radiosensitivity from tumor fibroblasts in order to estimate tumor response.
已发现皮肤成纤维细胞的体外放射敏感性在个体间存在差异，并且多项研究还表明，该参数与临床放射治疗中辐射诱导的晚期损伤相关。此外，已知某些遗传疾病会影响放射敏感性，例如，共济失调毛细血管扩张症基因纯合或杂合患者的正常组织在体内和体外均对辐射表现出异常敏感性。因此，人们认为存在一个由基因决定的成分，导致个体细胞产生特定的内在辐射反应。为了研究特定患者不同细胞之间的这种可能关系，我们建立了八对皮肤和肿瘤成纤维细胞培养物。供体患者患有子宫腺癌或头颈部鳞状细胞癌（SCC）。这些菌株的放射敏感性通过96孔板克隆形成试验来确定，我们之前曾用该试验对癌细胞进行放射敏感性测试。通过配对比较，发现八例中有五例两种成纤维细胞株在2.0 Gy照射后存活细胞分数（SF2）的值处于同一水平。在患者6中，肿瘤成纤维细胞的SF2显著高于皮肤成纤维细胞（P = 0.0014）。在另外两例中趋势相同，但无统计学意义。作为两组，两种类型的成纤维细胞彼此无差异，平均SF2值分别为0.24±0.07和0.21±0.05。SCC患者肿瘤成纤维细胞的SF2被证明显著高于腺癌患者（P = 0.030）。这些初步结果表明，肿瘤成纤维细胞的体外放射敏感性在许多情况下与正常细胞敏感性相关，但并非在所有情况下都如此。肿瘤成纤维细胞的放射敏感性似乎也遵循相应组织学类型肿瘤细胞的体外放射敏感性水平。需要进一步研究以更精确地确定肿瘤细胞和肿瘤成纤维细胞放射敏感性之间的关系，从而评估通过检测肿瘤成纤维细胞的放射敏感性来估计肿瘤反应的可能性。
