CARCINOGENESIS OF MAMMALIAN CELLS IN CULTURE

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类淋巴母细胞系， 以及在培养物中或体内转化的肿瘤细胞， 用于评价辐射引起的 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。 增加 X射线照射后染色单体损伤的发生率，特别是 在细胞周期的G-2期， 易患癌症和肿瘤转化， 为癌症的遗传易感性测试提供了基础。 目前正努力开发这样的细胞遗传学方法， 使用皮肤成纤维细胞、外周血淋巴细胞或 淋巴母细胞样细胞系。 这种现象的基因基础 基因定位于特定染色体的放射敏感性 从体细胞杂种，近交系 小鼠和同类小鼠品系;研究正在进行中， 定位和绘制这些基因位点。 染色体辐射敏感性 似乎是由G-2期DNA修复缺陷引起的。 另一 这个项目的一个方面是开发一个可复制的转换 以人表皮角质形成细胞作为体外模型， 随着生物学、细胞形态学和 生化电荷导致肿瘤转化， 特别强调DNA修复缺陷的获得 基因不稳定性。

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, are utilized in evaluating the relationship between radiation-induced chromosomal DNA damage, deficient DNA repair, genetic instability, cancer susceptibility and neoplastic transformation. An increased incidence of chromatid damage after x-irradiation, specifically during G-2 phase of the cell cycle, 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 a cytogenetic assay using skin fibroblasts, peripheral blood lymphocytes or lymphoblastoid cell lines. A genetic basis for this radiosensitivity with localization of genes to specific chromosomes is indicated from studies with somatic cell hybrids, inbred strains of mice and congenic mouse strains; studies are in progress to localize and map such gene loci. The chromosomal radiosensitivity appears to result from deficient DNA repair during G-2. Another aspect of this project is to develop a reproducible transformation system with human epidermal keratinocytes as an in vitro model for following the progression of biologic, cytomorphologic and biochemical charges leading to neoplastic transformation, with particular emphasis on the acquisition of DNA repair deficiencies and genetic instability.