ROLE OF TUMOR SUPPRESSOR GENES AND ONCOGENS IN CHEMICAL CARCINOGENESIS

人类和动物的癌症发展是一个多步骤的过程， 至少两类基因，即原癌基因和肿瘤抑制基因。 我们已经证明叙利亚仓鼠胚胎细胞的肿瘤转化 (SHE)在培养中是一个多步骤的过程， 原癌基因和肿瘤抑制基因的失活。损失或 肿瘤抑制基因的失活是肿瘤发生的关键步骤。 SHE细胞的多步肿瘤转化。非致瘤性变体 已被隔离，已失去（sup-）或保留（sup+）的能力， 抑制细胞杂合体中肿瘤细胞的致瘤性。sup+或的融合 不同肿瘤细胞的超变体显示出不同的模式， 抑制表明，一个家庭的肿瘤抑制基因存在于 这些成纤维细胞。目前，克隆肿瘤的几种策略 抑制基因正在进行中。sup+仓鼠细胞的cDNA文库具有 用来自sup+或sup-细胞的RNA筛选并差异表达 cDNA已被克隆。蛋白质的二维凝胶分析显示， 原肌球蛋白I表达的减少与 肿瘤抑制功能的丧失。一种细胞表型， 也发现了肿瘤抑制基因功能的丧失。 悬浮在琼脂中对转化和正常生长的可逆反应 因子在琼脂中形成集落，而sup+细胞不能生长，肿瘤 抑制基因可以通过导入 通过微细胞融合将正常染色体导入肿瘤细胞。我们已经证明 正常人11号染色体抑制宫颈癌细胞，肺 腺癌细胞、横纹肌肉瘤细胞和Wilms肿瘤细胞， 而3号染色体抑制肾癌和肺腺癌， 细胞一个子宫内膜癌细胞被三种不同的 染色体（Nos. 1、6和9）。除了肿瘤抑制基因 在某些永生细胞系中表达的上述基因， 致瘤性也可能受到细胞衰老的限制。我们的结果 表明可能参与衰老表型的基因可以 被定位在人类1号染色体上

Cancer development in humans and animals is a multistep process involving at least two classes of genes, proto-oncogenes and tumor suppressor genes. We have shown that neoplastic transformation of Syrian hamster embryo cells (SHE) in culture is a multistep process involving both activation of proto-oncogenes and inactivation of a tumor suppressor gene. The loss or inactivation of tumor suppressor genes is an essential step in the multistep neoplastic transformation of SHE cells. Non-tumorigenic variants have been isolated that have lost (sup-) or retained (sup+) the ability to suppress tumorigenicity of tumor cells in cell hybrids. Fusions of sup+ or sup- variants with different tumor cells show different patterns of suppression indicating that a family of tumor suppressor genes exists in these fibroblast cells. Currently, several strategies to clone tumor suppressor genes are in progress. cDNA libraries of sup+ hamster cells have been screened with RNA from sup+ or sup- cells and differentially expressed cDNAs have been cloned. Two-dimensional gel analyses of proteins showed that a reduction in the expression of tropomyosin I correlates with the loss of the tumor suppressor function. A cellular phenotype associated with the loss of tumor suppressor gene function has also been found. Sup- cells suspended in agar respond reversibly to transforming and normal growth factors by forming colonies in agar whereas sup+ cells fail to grow., Tumor suppressor genes can be mapped to specific chromosomes by introduction of normal chromosomes into tumor cells by microcell fusion. We have shown that normal human chromosome 11 suppresses cervical carcinoma cells, lung adenocarcinoma cells, rhabdomyosarcoma cells, and Wilms' tumor cells, whereas chromosome 3 suppresses renal carcinoma and lung adenocarcinoma cells. An uterine endometrial cancer cell was suppressed by three different chromosomes (Nos. 1, 6, and 9). In addition to the tumor suppressor genes described above that are expressed in some immortal cell lines, tumorigenicity also may be limited by cellular senescence. Our results indicate that a gene(s), possibly involved in the senescence phenotype, can be mapped to human chromosome 1.