Sanford K K, Parshad R, Price F M, Tarone R E, Schapiro M B
Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Cancer Genet Cytogenet. 1993 Oct 1;70(1):25-30. doi: 10.1016/0165-4608(93)90127-8.
Frequencies of chromatid aberrations in response to G2-phase x-irradiation were compared in PHA-stimulated blood lymphocytes from healthy control subjects, Down syndrome (DS) patients, and Alzheimer disease (AD) patients. In cells arrested with Colcemid immediately (0-30 min) after x-irradiation, DS, AD, and control cells showed similar high frequencies of chromatid breaks and gaps, representing unrepaired DNA strand breaks. Frequencies had decreased in AD and control cells arrested 30-90 min after irradiation. However, DS cells had two- to three-fold higher frequencies than AD or control cells. This result indicates deficient repair of the DNA damage in DS cells. Similar responses were obtained with lymphocytes from four of seven DS parents tested and with skin fibroblasts from DS patients compared to age-matched controls. Addition of 1-beta-D-arabinofuranosylcytosine (ara-C), an inhibitor of the repair polymerase, after x-irradiation during G2 phase increased the frequencies of chromatid breaks and gaps in lymphocytes from control and AD donors significantly more than in those from DS patients. This result indicates a deficiency in DS cells in incision at sites of x-ray-induced damage. Thus DS, like other cancer-prone genetic disorders, has a G2-phase DNA repair deficiency in strand break repair and also a second DNA repair deficiency in incision activity.
比较了健康对照受试者、唐氏综合征（DS）患者和阿尔茨海默病（AD）患者经PHA刺激的血液淋巴细胞中，G2期X射线照射后染色单体畸变的频率。在X射线照射后立即（0 - 30分钟）用秋水仙酰胺阻滞的细胞中，DS、AD和对照细胞显示出相似的高频率染色单体断裂和裂隙，代表未修复的DNA链断裂。照射后30 - 90分钟阻滞的AD和对照细胞中频率降低。然而，DS细胞的频率比AD或对照细胞高两到三倍。这一结果表明DS细胞中DNA损伤修复存在缺陷。在测试的七名DS患者父母中的四名的淋巴细胞以及DS患者的皮肤成纤维细胞与年龄匹配的对照相比，获得了类似的结果。在G2期X射线照射后添加修复聚合酶抑制剂1-β-D-阿拉伯呋喃糖基胞嘧啶（ara-C），对照和AD供体淋巴细胞中染色单体断裂和裂隙的频率增加幅度明显大于DS患者的淋巴细胞。这一结果表明DS细胞在X射线诱导损伤部位的切口存在缺陷。因此，DS与其他易患癌症的遗传疾病一样，在链断裂修复方面存在G2期DNA修复缺陷，并且在切口活性方面也存在第二种DNA修复缺陷。
