It is the primary purpose of this project to study some of the pertinent factors which influence cell differentiation and malignant transformation, using techniques and approaches which range from the microscopic to the molecular level. Particular emphasis is given to those systems in which murine RNA tumor viruses or chemical carcinogens may be the transforming agent. A variety of mouse model systems are used, including methylcholanthrene-induced sarcomas, plasma cell tumors, mammary tumors, and neuroblastomas. Current projects include: 1) effects of interferon on methylcholanthrene-induced sarcomas of the BALB/c mouse with the aim of defining antitumor activity and relationship to immune response; and 2) effects of interferon treatment on NIH 3T3 cells transfected with various (Ha) ras related oncogenes. Our results suggest that the major effects of interferon on chemically-induced sarcomas do not appear to be mediated through anticellular activity, but are related to the immune response in the host animal. A number of experiments confirm the necessity of functional T cells in order for interferon to exert its antitumor effect. Since interferon increases the expression of H-2 antigens on these tumor cells, this may serve to enhance their recognition by host T cells. NIH 3T3 cells were transfected with either cellular or viral Ha-ras genes prior to interferon treatment. In most of the cell lines examined, interferon inhibited cell growth, reduced cloning efficiency and delayed, but did not prevent, tumors in nude mice. When in vitro oncogene expression was measured at the mRNA level, c-Ha-ras mRNA was reduced by 2 to 4 fold following interferon treatment, while the mRNA for H-2 antigen was increased by 3-4 fold.
