RADIATION & CHEMICAL IN VITRO MALIGNANT TRANSFORMATION

辐射

• 批准号: 3481940
• 负责人: ANN R KENNEDY
• 金额: $ 47.84万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-12-15 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3481940
• 关键词: 3T3 cells; DNA repair; X ray; antioxidants; carcinogenesis inhibitor; cell growth regulation; cellular oncology; chemical carcinogen; chemoprevention; clone cells; diploidy; environment related neoplasm /cancer; environmental radiation; free radical oxygen; gene expression; genetic mapping; ionizing radiation; laboratory mouse; laboratory rat; neoplastic transformation; nonenzyme proteolytic agent; nucleic acid sequence; oncogenes; physical chemical interaction; protease inhibitor; proteolysis; radiation carcinogen; radiation carcinogenesis; radiation sensitivity; radiobiology; tissue /cell culture; ultraviolet radiation

The basic objective of this research project is to gain further information about the mechanism of radiation carcinogenesis induced by x-rays or UV light in in vitro assay systems. We will investigate interactions between radiation and chemical agents in the induction of malignant transformation in vitro. The specific chemical agents we are studying have known interactive effects on carcinogenesis in vivo, and have been observed to enhanced or suppress the induction of malignant cells in vitro by radiation. Many of the studies will be focussed on the mechanism(s) for the observed suppressive effects of protease inhibitors on malignant transformation induced by radiation. Studies on the mechanisms involved in the induction of radiation transformation and its modification by chemical agents in an in vitro system, in which cellular proliferation and other environmental conditions can be precisely controlled, should yield much information about the mechanisms involved in radiation induced cancer. Specifically, during the present grant period we will attempt to determine whether the following phenomena are involved in radiation transformation in vitro and its modification by chemical agents: oncogenes (involving studies on myc and ras), amplification of specific DNA sequences, proteoltyic activity (Boc-val-pro-arg-MCA hydrolyzing activity), free radical intermediates and growth factor processing. We plan to utilize several different in vitro transformation system in our studies including rat embryo fibroblasts. NIH 3T3 cells and human diploid (1522) cells, but most of our transformation studies will continue to be performed in C3H10T1/2 cells. In addition to our studies designed to determined the mechanisms involved in radiation transformation and its modification by chemicals, our studies also have a practical aim. Many of our studies will be performed with compounds which show promise as human cancer chemopreventive agents, with the aim of evaluating them for use as nontoxic dietary supplements to prevent the development of cancer in human populations.

这项研究项目的基本目标是获得进一步的 关于辐射致癌机制的信息 在体外检测系统中由X射线或紫外光诱导。我们会 研究辐射与化学物质之间的相互作用 在体外诱导恶性转化。这个 我们正在研究的特定化学试剂已知相互作用 对体内致癌的影响，并已观察到 增强或抑制体外恶性细胞的诱导 辐射。许多研究将集中在 观察到的蛋白酶抑制作用的机制(S) 辐射诱发恶性转化的抑制药。 辐射诱导机制的研究进展 In中的相变及其化学试剂的改性 体外系统，在该系统中，细胞增殖和其他 环境条件是可以精确控制的，应该 提供了有关以下机制的详细信息 辐射诱发的癌症。具体地说，在目前的赠款期间 在此期间，我们将尝试确定以下内容是否 在体外辐射转化中涉及的现象和 由化学试剂修饰：癌基因(涉及 Myc和ras的研究)，特异DNA的扩增 序列，蛋白活性(Boc-Val-Pro-Arg-MCA 水解性)、自由基中间体与生长 因素处理。我们计划在体外利用几种不同的 我们研究中的转化系统，包括大鼠胚胎 成纤维细胞。NIH 3T3细胞和人类二倍体(1522)细胞，但 我们的大部分转型研究将继续进行 在C3H10T1/2细胞中。除了我们的研究旨在 确定了辐射转化中涉及的机制 和它的化学修饰，我们的研究也有一个 实用的目标。我们的许多研究都将在 有望成为人类癌症的化合物 化学预防药物，目的是评估它们的使用情况 作为无毒的膳食补充剂，预防糖尿病的发生 人类中的癌症。