CANCER CHEMOTHERAPY AT TRANSCRIPTIONAL LEVEL

拟议研究的目的是研究癌症的化疗。 基因转录水平。 为了实现这一目标，RNA裂解酶及其启动因子将是 从鸡成髓细胞白血病细胞中提纯至均一。这个 从白血病细胞和正常细胞中提纯的酶将与 关于它们的性质、功能、亚单位结构和 重组，并进行RNA分析。预计这将提供 白血病特异性RNA聚合酶的进一步证据。纯化的RNA 将研究聚合酶启动因子以确定其性质， 生理功能及其刺激细胞生长的机制 RNA合成的启动。还将尝试确定其 其他正常和恶性细胞的活性(正常鸡成髓细胞 细胞，禽成髓细胞增多症病毒非产生细胞系，人白血病和 人淋巴瘤细胞系)。这些研究将揭示这一因素 对癌细胞生长的基因表达是特异的还是 真核细胞的RNA合成所普遍需要的。 同时使用几种目前使用的和较新的实验抗肿瘤药物 将研究药物对肿瘤基因的抑制作用 抄写。这项建议中使用的药物包括阿霉素和 6-硫代嘌呤及其衍生物(公元32、公元41、公元143和甲基化 硫代嘌呤类)。拟议研究的最终目标是 确定是否有可能阻止癌细胞的肿瘤表达 在转录水平上选择性地抑制 恶性RNA聚合酶(或其调节因子)在不影响 正常的酶。

The aim of the proposed research is to study the chemotherapy of cancer at the level of gene transcription. To achieve this goal RNA prolymerase and its initiation factor will be purified from chicken myeloblastosis leukemic cells to homogeneity. The purified enzymes from leukemic as well as normal cells will be studies with regard to their properties, functions, subunit structures and reconstitution, and produce RNA analysis. This is expected to provide further evidence for a leukemic-specific RNA polymerase. The purified RNA polymerase initiation factor will be studied to determine its properties, physiological functions and the mechanism by which it stimulates the initiation of RNA synthesis. Attempts will also be made to determine its activity in other normal and malignant cells (normal chicken myeloblast cells, avian myeloblastosis viral nonproducer cell line, human leukemic and human lymphoma cell lines). These studies will reveal whether the factor is specific for the gene expression of cancerous growth or it is universally required for the RNA synthesis of eukaryotic cells. Concurrently several currently used and newer experimental antineoiplastic agents will be studied for their inhibitory effects on neoplastic gene transcription. The agents used in this proposal include adriamycin and 6-mercaptopurine and their derivative (AD 32, AD 41, AD 143, and methylated mercaptopurines). The ultimate goal of the proposed research is to determine if it is possible to arrest neoplastic expression of cancer cells at transcriptional level by selectively inhibiting the activity of malignant RNA polymerase (or its regulatory factor) without affecting the normal enzyme.