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

任何细胞毒剂的治疗都可以触发肿瘤中存活的细胞比以前更快地分裂。这种现象被广泛认为是“人口再繁殖”。为了更好地阐明这一机制，我们进行了基因表达谱和病理实验。以小鼠纤维肉瘤细胞株QRsP为研究对象。用10Gy射线照射细胞。进行菌落鉴定和克隆。建立了6个无性系。对第2次10Gy射线照射后克隆数最多的克隆进行了cDNA分析。然后进行小鼠移植实验。CDNA分析表明，耐受克隆的细胞周期蛋白依赖性激酶抑制因子p16和p57表达下调，分别是耐受克隆的14.8倍和12.0倍。基质金属蛋白酶3和13表达上调，分别为22.5倍和25.8倍。耐性克隆的移植成功率为100%(5/5)，亲本为40%(2/5)。光镜下，亲本平均有丝分裂细胞数为4.0+/-3.9，耐性无性系为12.8+/-3.4(p&lt；0.01，学生t检验)。这项研究表明，种群再繁殖不是对辐射的暂时反应。它可能是由“克隆性”基因表达变化引起的，尽管目前尚不清楚这些变化是由于耐受细胞选择还是基因突变/修饰所致。

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.