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.
