STUDIES ON THE ACTIVATION OF ONCOGENES IN VIRUSES AND HUMAN TUMORS

我们已经分离出一种NIH 3 T3成纤维细胞系， 在不存在蛋白质生长因子的培养基中。 这些细胞似乎 释放能够诱导无血清生长的可溶性因子 正常NIH 3 T3细胞，以及几个正常的人二倍体 成纤维细胞 这些自发选择的3 T3细胞系， 在3 T3细胞系中以非常低的频率出现， 与ets-I和ets-2基因诱导的明显不同 和myb-ets融合癌基因，这表明多种机制， 可用于消除3 T3成纤维细胞中的血清依赖性。 我们已经测试了人类白血病的DNA含有4：11和8：21 可转染序列的易位，其可以显性改变 形态学、致瘤性或3 T3成纤维细胞的血清依赖性。 的 这些DNA中的大多数在多次测定中不含可检测的活性， 提示这些易位不会产生显性癌基因， 可通过DNA转染检测。 我们已经产生了一系列CHO细胞系，其携带单个人类 含有药物选择性标记的染色体。 这样的细胞系将 可用作特定染色体的供体，以确定 能够抑制已建立的转化表型的基因 人类肿瘤细胞。

We have isolated an NIH3T3 fibroblast cell line which grows in defined media in the absence of protein growth factors. The cells appear to release soluble factors which are capable of inducing serum-free growth of normal NIH3T3 cells, as well as several normal human diploid fibroblasts. These spontaneously-selected 3T3 cell lines, which appear to arise at very low frequency in 3T3 cell lines, express a phenotype clearly distinguishable from that induced by the ets-I and ets-2 genes and the myb-ets fusion oncogene, suggesting that multiple mechanisms are available for abrogation of serum dependence in 3T3 fibroblasts. We have tested DNAs from human leukemias containing 4:11 and 8:21 translocations for transfectable sequences which can dominantly alter the morphology, tumorigenicity, or serum dependence of 3T3 fibroblasts. The majority of these DNAs contain no detectable activity in multiple assays, suggesting that these translocations do not generate dominant oncogenes detectable by DNA transfection. We have generated a series of CHO cell lines carrying single human chromosomes which contain drug-selectable markers. Such cell lines will be useful as donors of specific chromosomes to determine the presence of genes capable of suppressing the transformed phenotype of established human tumor cells.