RAS GENE MUTATION TIME AND STRUCTURE IN MOUSE LYMPHOMAS

我们将继续研究小鼠诱导胸腺的模型系统 致癌物质导致的淋巴瘤。因为我们已经证明了 K和N-ras癌基因一直与这些肿瘤相关，我们 会首先集中分析两者之间的平衡或不平衡 这些肿瘤中突变的等位基因和正常的等位基因。我们会 也研究了小鼠N-ras癌基因的结构决定数目 利用体外实验定位其未翻译的外显子及其功能 诱变和基因转移。我们将处理这个有争议的问题 Ras是肿瘤发生的早期或晚期事件 将单个供者的白血病前期细胞移植到多个供者 受者和分析继发肿瘤是否都有相同的癌基因 突变。最后，从概念上讲，与前面的实验相关 将尝试创造具有激活的N-ras癌基因的转基因小鼠， 在可诱导启动子的影响下，来确定它是否可以，单独 或者与其他因素结合在一起，当它发生时会产生恶性肿瘤 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.