MECHANISMS OF NEOPLASTIC TRANSFORMATION IN CULTURED HUMAN CELLS

我们比较了两种遗传病的细胞反应， Cockayne综合征(CS)与色素性干皮病互补组 C(XP-C)，两者都表现出细胞对阳光的过敏性， 但其中只有一种，XP，表现出高比率的阳光诱导 癌症。与XP细胞相比，CS细胞表现出正常的G2反应 用x射线或近紫外线可见光照射。然而，CS 细胞对光造成的DNA损伤的修复能力不足 在细胞周期的S和G1期。目前的结果支持 G2期DNA修复缺陷的概念在 致癌。在G1之后添加DNA修复抑制物咖啡因 光暴露对正常人染色单体断裂或缝隙几乎没有影响 但CS的染色单体断裂频率显著增加 单元格和XP单元格中的断裂和间隙。结果提示：CS 而XP非周期细胞，如神经元，可能会积累损伤， 周期皮肤成纤维细胞将在S和G2期修复。 因此，CS和XP的修复缺陷可能是神经学上的原因 与这两种遗传病相关的退化。在…方面的不足 DNA修复，表现为G2期后持续的染色单体损伤 辐射，是自发获得的或由ras癌基因诱导的 连续培养的人乳腺上皮细胞系 与他们的恶性转化有关。AS 先前报道的人表皮角质形成细胞(癌症相关基因 1987；47：1390)，修复缺陷表型的获得似乎 是恶性转化过程中的早期必要步骤 培养中的人类细胞。

We have compared responses of cells from two genetic disorders, Cockayne's syndrome (CS) and xeroderma pigmentosum complementation group C (XP-C), both of which exhibit cellular hypersensitivity to sunlight, but only one of which, XP, manifests a high rate of sunlight-induced cancer. CS cells, in contrast to XP cells, showed a normal G2 response to irradiation with either x-rays or near-UV visible light. However, CS cells showed a deficiency in repair of DNA damage inflicted by light during S and G1 phases of the cell cycle. The present results support the concept that deficient DNA repair during G2 phase plays a role in carcinogenesis. Addition of the DNA repair inhibitor, caffeine, after G1 light exposure had little effect on chromatid breaks or gaps in normal cells but significantly increased frequencies of chromatid breaks in CS cells and both breaks and gaps in XP cells. The results suggest that CS and XP noncycling cells, such as neurons, may accumulate damage that in cycling skin fibroblasts would be repaired during S and G2 phases . Thus, the repair deficiencies in CS and XP may account for the neurologic degeneration associated with these two genetic diseases. A deficiency in DNA repair, manifest as persistent chromatid damage after G2 phase x- irradiation, was acquired spontaneously or induced by ras oncogene in continuous lines of human mammary epithelial cells in culture prior to or in association with their malignant neoplastic transformation. As reported previously for human epidermal keratinocytes (Cancer Res 1987;47:1390), acquisition of the repair-deficient phenotype appears to be an early requisite step in the malignant neoplastic transformation of human cells in culture.