The secret of radiation-surviving cell : multidisciplinary approach to eradicate cancer

用任何细胞毒性药物治疗都能促使肿瘤中存活的细胞比以前分裂得更快。这种现象被广泛认为是“人口再生”。为了更好地阐明其机制，我们进行了基因表达谱和病理实验。使用小鼠纤维肉瘤细胞系QRsP。细胞以10 Gy照射。进行菌落测定和克隆。建立了6个无性系。对第2次10 Gy辐照时菌落数量最多的克隆进行cDNA分析。然后进行小鼠移植实验。cDNA分析显示，细胞周期蛋白依赖性激酶抑制剂p16和p57下调；耐受性克隆分别为14.8倍和12.0倍。基质金属蛋白酶3、13表达上调；分别是22.5倍和25.8倍。耐受性克隆移植率为100%(5/5)，而亲本移植率为40%（2/5）。光镜下，亲本平均有丝分裂细胞数为4.0+/-3.9个，耐受性无性系平均有丝分裂细胞数为12.8+/-3.4个（p<0.01, Student’st检验）。这项研究表明，重新繁殖不是对辐照的暂时反应。它可能是由“克隆”基因表达变化引起的，尽管尚不清楚这种变化是由于耐受细胞选择还是基因突变/修饰。

Treatment with any cytotoxic agent can trigger surviving cells in a tumor to divide faster than before. This phenomenon is widely recognized as "repopulation". To better clarify the mechanism, gene expression profiling and pathological experiments were performed. A mouse fibrosarcoma cell line, QRsP, was used. Cells were irradiated with 10 Gy. Colony assay and cloning were performed. Six clones were established. cDNA analysis was performed on the clone that showed the largest number of colonies on the 2nd 10 Gy irradiation. Mouse transplantation experiment was then carried out. cDNA analysis showed that cyclin-dependent kinase inhibitors, p16 and p57 were down-regulated ; 14.8- and 12.0-fold, respectively for the tolerant clone. Matrix metalloproteinase 3 and 13 were up-regulated ; 22.5- and 25.8-fold, respectively. Transplantation ratio was 100% (5/5) for the tolerant clone whereas it was 40% (2/5) for the parent. Under light microscope, the mean mitotic cell number was 4.0+/-3.9 for the parent, and 12.8+/-3.4 for the tolerant clone (p<0.01, Student's t-test). This study implies that repopulation is not a temporary reaction to irradiation. It is caused probably by "clonal" gene-expression changes, though it remains unknown whether the changes are attributable to tolerant cell selection or to gene mutation/modification.