Brachman D G, Beckett M, Graves D, Haraf D, Vokes E, Weichselbaum R R
Department of Radiation and Cellular Oncology, University of Chicago Hospitals, Illinois 60637.
Cancer Res. 1993 Aug 15;53(16):3667-9.
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.
肿瘤对放射治疗反应的分子基础目前仍知之甚少。最近的证据表明，p53肿瘤抑制基因可能参与了X射线照射导致DNA损伤后出现的G1期阻滞的产生。进一步有人提出，缺乏p53检查点功能的肿瘤细胞可能对X射线照射导致的细胞杀伤更敏感，因为这些细胞尽管DNA损伤未修复仍进入S期。我们通过将24种头颈鳞状细胞癌细胞系的体外2 Gy存活分数与突变状态相关联，来检验p53突变的肿瘤细胞对放射更敏感这一假设。24个肿瘤中有15个（63%）存在p53突变；所有突变均为发生在外显子5至9内的纯合变化。有突变组的2 Gy存活分数为0.568，无突变肿瘤的存活分数为0.507（曼-惠特尼检验，P = 0.28）。此外，未观察到放射敏感性与突变类型、密码子位置或预测的氨基酸改变之间存在关联。我们的数据不支持p53基因改变使肿瘤细胞更易因辐射而增加细胞杀伤这一假设。
