Hansson J, Keyse S M, Lindahl T, Wood R D
Imperial Cancer Research Fund, South Mimms, Herts, United Kingdom.
Cancer Res. 1991 Jul 1;51(13):3384-90.
Whole cell extracts from human lymphoid cell lines can perform in vitro DNA repair synthesis in plasmids damaged by agents including UV or cis-diamminedichloroplatinum(II) (cis-DDP). Extracts from xeroderma pigmentosum (XP) cells are defective in repair synthesis. We have now studied in vitro DNA repair synthesis using extracts from lymphoblastoid cell lines representing four human hereditary syndromes with increased sensitivity to DNA-damaging agents. Extracts of cell lines from individuals with the sunlight-sensitive disorders dysplastic nevus syndrome or Cockayne's syndrome (complementation groups A and B) showed normal DNA repair synthesis in plasmids with UV photoproducts. This is consistent with in vivo measurements of the overall DNA repair capacity in such cell lines. A number of extracts were prepared from two cell lines representing the variant form of XP (XP-V). Half of the extracts prepared showed normal levels of in vitro DNA repair synthesis in plasmids containing UV lesions, but the remainder of the extracts from the same cell lines showed deficient repair synthesis, suggesting the possibility of an unusually labile excision repair protein in XP-V. Fanconi's anemia (FA) cells show cellular hypersensitivity to cross-linking agents including cis-DDP. Extracts from cell lines belonging to two different complementation groups of FA showed normal DNA repair synthesis in plasmids containing cis-DDP or UV adducts. Thus, there does not appear to be an overall excision repair defect in FA, but the data do not exclude a defect in the repair of interstrand DNA cross-links.
来自人淋巴样细胞系的全细胞提取物能够在受到包括紫外线或顺二氨二氯铂（II）（顺铂）等试剂损伤的质粒中进行体外DNA修复合成。着色性干皮病（XP）细胞的提取物在修复合成方面存在缺陷。我们现在使用来自代表四种对DNA损伤剂敏感性增加的人类遗传综合征的淋巴母细胞系提取物，研究了体外DNA修复合成。来自患有日光敏感疾病发育异常痣综合征或科凯恩综合征（互补组A和B）的个体的细胞系提取物，在含有紫外线光产物的质粒中显示出正常的DNA修复合成。这与此类细胞系中整体DNA修复能力的体内测量结果一致。从代表XP变异型（XP-V）的两个细胞系中制备了许多提取物。所制备的提取物中有一半在含有紫外线损伤的质粒中显示出正常水平的体外DNA修复合成，但来自同一细胞系的其余提取物显示出修复合成缺陷，这表明XP-V中可能存在一种异常不稳定的切除修复蛋白。范可尼贫血（FA）细胞对包括顺铂在内的交联剂表现出细胞超敏性。来自属于FA两个不同互补组的细胞系的提取物，在含有顺铂或紫外线加合物的质粒中显示出正常的DNA修复合成。因此，FA似乎不存在整体切除修复缺陷，但这些数据并不排除链间DNA交联修复存在缺陷的可能性。
