Pulkkinen J O, Servomaa K, Pekkola K, Kulmala J, Grenman R
Department of Otorhinolaryngology, University of Turku, Finland.
Anticancer Res. 2000 May-Jun;20(3A):1503-11.
It was our intention to enlighten the controversy between the mainstream of studies and our previous results showing a correlation between the intrinsic radiosensitivity and the p53 allele status of 20 human head and neck squamous cell carcinoma (HNSCC) cell lines. In our study cell lines carrying a wild-type (WT) p53 allele were significantly more radioresistant than cell lines which lacked a WT gene. We observed nine HNSCC cell lines with known intrinsic radiosensitivity and p53 allele status with time-lapse video microscopy after irradiation with 2 and 3 Gy. We studied the mitotic and apoptotic frequencies and scored the apoptoses as to whether they occurred morphologically in mitosis or in interphase. Irradiation with 2 or 3 Gy did not induce apoptosis in the cell lines studied. As expected the mitotic frequency was reduced by the irradiation. This was statistically significant in the cell lines which were radiosensitive when measured with a clonogenic assay. p53 allele status did not have an independent effect on the cell lines, except that the irradiation favoured the apoptosis in mitosis in the cell lines with WT p53 and the apoptosis in the interphase in the cell lines with a mutated or non-functional p53 gene. We conclude that although the apoptosis is not induced by irradiation with 2 Gy or 3 Gy, the p53 suppressor gene seems to influence the process of apoptosis after irradiation in the cell lines studied.
我们旨在阐明主流研究与我们之前的结果之间的争议,我们之前的结果显示,20种人类头颈部鳞状细胞癌(HNSCC)细胞系的内在放射敏感性与p53等位基因状态之间存在相关性。在我们的研究中,携带野生型(WT)p53等位基因的细胞系比缺乏WT基因的细胞系对辐射的耐受性明显更高。我们用延时视频显微镜观察了9种已知内在放射敏感性和p53等位基因状态的HNSCC细胞系在接受2 Gy和3 Gy照射后的情况。我们研究了有丝分裂和凋亡频率,并对凋亡进行评分,以确定它们是在有丝分裂期还是在间期发生形态学变化。2 Gy或3 Gy的照射并未在所研究的细胞系中诱导凋亡。正如预期的那样,照射降低了有丝分裂频率。在用克隆形成试验测量时,这在放射敏感的细胞系中具有统计学意义。p53等位基因状态对细胞系没有独立影响,只是照射有利于携带WT p53的细胞系在有丝分裂期发生凋亡,而有利于携带突变或无功能p53基因的细胞系在间期发生凋亡。我们得出结论,虽然2 Gy或3 Gy的照射不会诱导凋亡,但p53抑癌基因似乎会影响所研究细胞系照射后的凋亡过程。