MECHANISMS OF CARCINOGENESIS AND NEURODEGENERATION USING CULTURED CELLS

细胞遗传学检测在细胞分裂相期间细胞的DNA修复能力 细胞周期，特别是G1和G2。 G2修复 将测定应用于皮肤成纤维细胞或植物血凝素（PHA）。 刺激的遗传病患者外周血淋巴细胞 易患癌症 视网膜母细胞瘤（RB）的成纤维细胞系 与正常人相比， 对照组显示染色单体断裂的频率显著较高， 当检查0.5至1.5时，代表未修复的DNA链断裂的缺口 h。 PHA刺激血液的有限研究 淋巴细胞也显示出异常高的频率在未受影响的 RB基因缺陷携带者以及一个双边案件， 其中一个家长 结果表明， RB和正常细胞之间的频率不能解释为 细胞周期的差异扰动或G2期的差异 延迟 结果与处理DNA损伤的缺陷一致 在遗传性RB患者的细胞中。 另外。DNA修复能力 在G1和G2期间，在患者的皮肤成纤维细胞中检查 神经退行性疾病包括科凯恩综合征唐氏 综合征和阿尔茨海默病（AD）。后者既有家族性的， 在起源上是零星的。从细胞中去除DNA损伤的缺陷 患者。或注定要发展。阿尔茨海默病（AD）是 通过使用DNA修复抑制剂揭示。 缺陷可能是 致病性，并为症状前检测提供了依据， 设计治疗试验的基本原理。

A cytogenetic assay for DNA repair capacity of cells during phases of the cell cycle, particularly G1 and G2, has been developed. The G2 repair assay was applied to skin fibroblasts or Phytohemagglutinin (PHA)- stimulated peripheral blood lymphocytes from patients with genetic predisposition to cancer. Fibroblast cell lines from retinoblastoma (RB) patients with the hereditary form of disease compared with normal controls showed a significantly higher frequency of chromatid breaks and gaps representing unrepaired DNA strand breaks when examined 0.5 to 1.5 h after x-irradiation. Limited studies of PHA-stimulated blood lymphocytes also showed abnormally high frequencies in unaffected carriers of the defective RB gene. as well as in one bilateral case and one of the parents. It was shown that the difference in aberration frequencies between RB and normal cells cannot be explained by differential perturbation of the cell cycle or differences in G2 phase delay. The results are consistent with a defect in processing DNA damage in cells from hereditary RB patients. In addition. DNA repair capacities were examined both during G1 and G2 in skin fibroblasts from patients with neurodegenerative diseases including Cockayne's syndrome. Down's syndrome and Alzheimer's disease (AD). the latter both familial and sporadic in origin. Defective removal of DNA damage from cells of patients with. or destined to develop. Alzheimer's disease (AD) was revealed through use of DNA-repair inhibitors. The defect may be pathogenic and provides a basis for presymptomatic testing and a rationale for devising therapeutic trials.