MODULATION OF THE TUMORIGENICITY OF TRANSFORMED CELLS

这项申请是一项研究的继续，目的是检查 用两种肿瘤病毒之一在细胞和/或动物上的N-硝糖化合物， 猴病毒40(SV40)或单纯疱疹病毒2型(HSV-2)。两种制度 在申请者的实验室中可以找到研究的全部内容。第一个是In 仓鼠体内的共癌系统。新生的动物接受 SV40+亚硝胺乙基亚硝脲(ENU)可降低潜伏期 肿瘤发育期。对该系统的进一步描述是 想要。研究兴趣的第二个领域是对一个 疱疹病毒转化细胞系333-8-9，. 这就是酶-纤溶酶原激活物(PA)与 333-8-9细胞形成原发肿瘤和/或转移的能力 注射到同基因新生动物体内。人们认为，操纵 转化细胞群体中的PA水平将预测操作 这一特定细胞系的细胞致瘤性。这项研究建议 在此应用中打算实现几个主要目标。首先，SV40 和SV40/ENU来源的肿瘤进行比较和潜在的差异 细胞和病毒标志物和/或致瘤潜力将被注意到。 第二，病毒转化后的体外转化细胞系 或与病毒和致癌物的共转化将使用 与将用于比较体内肿瘤的标准类似。第三，我们 将尝试确认一个转换标记(PA)在 333-8-9用于预测致癌潜力，我们将尝试 表明与病毒的共转化加上化学物质会导致PA的改变 与仅用病毒进行的转化相比，水平更高。上一次我们 将证明PA水平的直接变化与已知肿瘤 启动子可以改变细胞的致瘤性，我们将尝试展示 致癌物可以促进病毒转化的细胞，其方式类似于 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.