p53 mutation does not correlate with radiosensitivity in 24 head and neck cancer cell lines.
p53 mutation does not correlate with radiosensitivity in 24 head and neck cancer cell lines.
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发表时间：
1993-08
期刊：
影响因子：
11.2
通讯作者：
David Brachman;Michael A. Beckett;D. Graves;D. Haraf;E. Vokes;R. Weichselbaum
中科院分区：
文献类型：
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作者：
David Brachman;Michael A. Beckett;D. Graves;D. Haraf;E. Vokes;R. Weichselbaum
肿瘤对放射治疗反应的分子基础还知之甚少。最近的证据表明，P53肿瘤抑制基因可能参与了X射线损伤DNA后出现的G1期停滞的产生。进一步提出，缺乏P53检查点功能的肿瘤细胞可能对X射线的杀伤更敏感，因为这些细胞尽管DNA损伤未修复，但仍进入S期。我们通过比较24株头颈部鳞状细胞癌细胞系的体外存活分数和突变状态，验证了P53基因突变的肿瘤细胞对辐射更敏感的假设。在24例肿瘤中有15例(63%)存在P53突变，均为发生在第5-9外显子的纯合子改变。有突变的肿瘤在2Gy时的存活分数为0.568，而无突变的肿瘤为0.507(P=0.28Mann-Whitney检验)。此外，辐射敏感性与突变类型、密码子位置或预测的氨基酸变化之间没有关联。我们的数据不支持这样的假设，即p53基因改变使肿瘤细胞容易通过辐射增加细胞杀伤力。
The molecular basis of tumor response to therapeutic radiation is poorly understood. Recent evidence suggests the p53 tumor suppressor gene may be involved in production of the G1 arrest seen following DNA damage by X-irradiation. It has further been proposed that tumor cells lacking the p53 checkpoint function are likely to be more sensitive to cell killing by X-irradiation because these cells enter S phase despite unrepaired DNA damage. We tested the hypothesis that tumor cells with p53 mutations are more radiosensitive by correlating the in vitro surviving fraction at 2 Gy with the mutational status of 24 head and neck squamous cell cancer cell lines. p53 mutations were present in 15 of 24 (63%) of tumors; all were homozygous changes occurring within exons 5-9. The surviving fraction at 2 Gy for the group with mutations was 0.568 compared to 0.507 for tumors without mutations (P = 0.28, Mann-Whitney test). Furthermore, no association between radiosensitivity and mutational type, codon location, or predicted amino acid alteration was noted. Our data do not support the hypothesis that p53 gene alteration predisposes tumor cells to increased cell killing via radiation.