RAS GENE MUTATION TIME AND STRUCTURE IN MOUSE LYMPHOMAS

我们将继续研究小鼠胸腺诱导的模型系统， 淋巴瘤的致癌剂。 因为我们已经证明， K和N-ras癌基因与这些肿瘤一致相关，我们 我将首先集中在分析的平衡或不平衡之间 突变的等位基因及其正常的对应部分。 我们将 还研究了小鼠N-ras癌基因的结构， 用体外细胞培养技术定位其非翻译外显子及其功能 诱变和基因转移。 我们将着手处理这个有争议的问题 ras是肿瘤发生的早期或晚期事件， 将来自单个供体的前白血病细胞移植到多个供体中， 接受者并分析随后的肿瘤是否具有相同的癌基因 突变 最后，在概念上与之前的实验相关， 将尝试制造具有激活的N-ras癌基因的转基因小鼠， 在诱导型启动子的影响下， 或与其他因素结合，产生恶性肿瘤时， 及时诱导表达。

We will continue to study the model system of murine induced thymic lymphomas by carcinogenic agents. Since we have already demonstrated that K and N-ras oncogenes are consistently associated with these tumors, we will concentrate first in the analysis of the balance or imbalance between the mutated, allele and its normal counteerpart in these tumors. We will study also the structure of the mouse N-ras oncogene determining the number and location of its untranslated exons and their function using in vitro mutagenesis and gene transfer. We will approach the controversial problem of ras being an early or late event in tumorigenesis by using transplantation of preleukemic cells from a single donor into several recipients and analyzing if the subseqent tumors have all the same oncogene mutation. Finally, and conceptually related to the previous experiments we will attempt to create transgenic mice with an activated N-ras oncogene, under the influence of an inducible promoter, to determine if it can, alone or in combination with other factors, produce malignancies when it is timely induced to express.