MODULATION OF THE TUMORIGENICITY OF TRANSFORMED CELLS

本申请是一项研究的延续， N-亚硝基化合物对具有两种肿瘤病毒之一的细胞和/或动物的作用， 猿猴病毒40（SV 40）或单纯疱疹病毒型（HSV-2）。 两制 申请人的实验室可提供研究报告。 第一个是in 仓鼠体内致癌系统。 新生动物接受 SV 40加亚硝酰胺乙基亚硝基脲（ENU）的潜伏期降低， 肿瘤发展的时期。 该系统的进一步表征是 需要的话 研究兴趣的第二个领域是研究一个 疱疹病毒转化细胞系333-8-9，. 即纤溶酶原激活物（PA）与 333-8-9细胞形成原发性肿瘤和/或转移瘤的能力 注射到同系新生动物中。 有人认为，操纵 转化细胞群中的PA水平将预测操作 细胞致癌性的最大值。 研究提出 本申请旨在实现几个主要目标。 首先，SV 40 和SV 40/ENU衍生的肿瘤进行比较， 细胞和病毒标志物和/或致瘤潜力。 第二，病毒转化后体外衍生的转化细胞系 或与病毒和致癌物的共转化将使用 与用于比较体内肿瘤的标准相似。 三是 我将尝试确认一个转化标记（PA）在 333-8-9细胞系预测肿瘤发生潜力，我们将尝试 表明与病毒和化学物质的共转化导致PA改变 与单独用病毒进行的转化相比， 最后我们 将证明已知肿瘤的PA水平的直接改变 启动子可以改变细胞的致瘤性，我们将试图表明， 致癌物质可以促进病毒转化细胞的方式类似于 已知的肿瘤促进剂。

This application is a continuation of a study to examine the effect of N-nitrose compounds on cells and/or animals with one of two tumor viruses, simian virus 40 (SV40) or herpes simplex virus type (HSV-2). Two systems of study are available in the applicant's laboratory. the first is an in vivo cocarcinogenesis system in hamsters. Newborn animals that receive SV40 plus the nitrosamide ethylnitrosourea (ENU) have a decreased latent period for tumor development. Further characterization of this system is desired. The second area of research interest is a study of one tumorigenic parameter of the herpesvirus transformed cell line 333-8-9,. that is the relationship of the enzyme plasminogen activator (PA) to the capability of 333-8-9 cells to form primary tumors and/or metastases after injection into syngeneic newborn animals. It is felt that manipulation of PA levels in the transformed cell population will predict the manipulation of cellular oncogenicity for this given cell line. The research proposed in this application intends to accomplish several major goals. First, SV40 and SV40/ENU derived tumors will be compared and potential differences in cell and virus markers and/or in tumorigenic potential will be noted. Second, transformed cells lines derived in vitro after virus transformation or cotransformation with viruses and carcinogens will be compared using similar criteria as will be used to compare the in vivo tumors. Third, we will try to confirm that one transformation marker (PA) is important in the 333-8-9 line for prediction of tumorigenic potential and we will try to show that cotransformations with viruses plus chemical result in altered PA levels compared to transformations carried out with virus alone. Last we will demonstrate that direct alteration of PA levels with known tumor promoters can alter cellular tumorigenicity and we will attempt to show that carcinogens can promote virally transformed cells in a way similar to known tumor promoters.