GENETIC PREDISPOSITION TO CANCER AND NEOPLASIA IN CULTURED CELLS

皮肤成纤维细胞、外周血淋巴细胞和 来自正常和癌症易感个体的淋巴母细胞系，以及 作为在培养物中或体内转化的肿瘤细胞， 评价辐射诱发的染色体DNA 损伤，DNA修复缺陷，遗传不稳定性，癌症易感性 和肿瘤转化。染色单体损伤的持续性 有丝分裂前的x射线照射与 癌症和肿瘤转化，并可以提供基础， 测试癌症遗传易感性。目前的努力方向是 为了开发这样一种使用皮肤成纤维细胞、外周血 淋巴细胞或类淋巴母细胞系。这种反应的遗传基础 基因定位于特定染色体的DNA损伤， 从体细胞杂交，小鼠近交系， 同源小鼠品系和微细胞融合染色体转移; 定位和绘制这些基因座的研究正在进行中。持续存在 染色单体损伤的发生似乎是由G2期DNA修复缺陷引起的。 该项目的另一个方面是在人类上皮细胞中跟踪 生物学变化进展导致肿瘤转化， 特别强调DNA修复缺陷的获得， 遗传不稳定性

Cultures of skin fibroblasts, peripheral blood lymphocytes and lymphoblastoid cell lines from normal and cancer-prone individuals, as well as neoplastic cells transformed in culture or in vivo, were utilized in evaluating the relationship between radiation-induced chromosomal DNA damage, deficient DNA repair, genetic instability, cancer susceptibility and neoplastic transformation. The persistence of chromatid damage after x-irradiation just before mitosis is associated with both a predisposition to cancer and neoplastic transformation, and can provide the basis of a test for genetic susceptibility to cancer. Efforts are currently directed toward developing such an assay using skin fibroblasts, peripheral blood lymphocytes or lymphoblastoid cell lines. A genetic basis for this response to DNA damage with localization of genes to specific chromosomes is indicated from studies with somatic cell hybrids, inbred strains of mice, congenic mouse strains and chromosome transfers by microcell fusion; studies are in progress to localize and map such gene loci. The persistence of chromatid damage appears to result from deficient DNA repair during G2. Another aspect of this project is to follow in human epithelial cells the progression of biologic changes leading to neoplastic transformation, with particular emphasis on the acquisition of DNA repair deficiencies and genetic instability.