Camplejohn R S, Perry P, Hodgson S V, Turner G, Williams A, Upton C, MacGeoch C, Mohammed S, Barnes D M
Richard Dimbleby Department of Cancer Research, UMDS, St Thomas' Hospital, London, UK.
Br J Cancer. 1995 Sep;72(3):654-62. doi: 10.1038/bjc.1995.390.
The cellular response, in terms of cell cycle arrest(s) and apoptosis, to radiation-induced DNA damage was studied. Experiments were performed on both mitogen-stimulated and resting peripheral blood lymphocytes (PBLs) from normal and cancer-prone (C-P) individuals. The C-P individuals comprised three patients carrying germline p53 mutations and three members of two families apparently without such mutations, but with an inherited defect which results in p53 deregulation as shown by high levels of stabilised p53 protein in normal tissues. Interestingly, mitogen-stimulated PBL, from both normal and C-P individuals failed to demonstrate a G1 arrest after gamma radiation. However, a clear difference was seen in the apoptotic response to DNA damage, of PBL from normal and C-P individuals; PBLs from C-P individuals with inherited p53-related defects had a reduced apoptotic response (P = 0.0003). There was a wide margin of separation, with no overlap between the two groups, supporting the possibility of using this altered apoptotic response as a screening test. This simple and rapid procedure could be used to identify those individuals in a C-P family who carry germline p53-related defects. The method appears to detect both individuals with p53 mutations and those apparently without mutations but with other p53-related defects.
研究了细胞对辐射诱导的DNA损伤在细胞周期停滞和凋亡方面的反应。对来自正常个体和癌症易感（C-P）个体的有丝分裂原刺激的和静息的外周血淋巴细胞（PBL）进行了实验。C-P个体包括三名携带种系p53突变的患者以及两个家族的三名成员，这两个家族显然没有此类突变，但存在一种遗传性缺陷，导致p53失调，如正常组织中稳定的p53蛋白水平升高所示。有趣的是，来自正常个体和C-P个体的有丝分裂原刺激的PBL在γ辐射后均未表现出G1期停滞。然而，在正常个体和C-P个体的PBL对DNA损伤的凋亡反应中观察到明显差异；具有遗传性p53相关缺陷的C-P个体的PBL凋亡反应降低（P = 0.0003）。两组之间有很大的分离度，没有重叠，这支持了将这种改变的凋亡反应用作筛选试验的可能性。这种简单快速的程序可用于识别C-P家族中携带种系p53相关缺陷的个体。该方法似乎既能检测出携带p53突变的个体，也能检测出明显没有突变但存在其他p53相关缺陷的个体。
