The long range purpose of this project is to investigate the roles of cellular oncogens and retroviruses in neoplasia, and to use viral mutants for elucidating the mechanism of regulation of gene expression associated with cell differentiation and oncogenesis. The topics of current interest are: 1) Oncogene rearrangement, amplification, and expression in human hepatocellular carcinomas, teratocarcinomas, choriocarcinomas, murine reticulum cell neoplasms, and trophoblastic tumors. Two human teratocarcinoma cell lines were found to have 3- to 4-fold amplification and rearrangement of Ki-ras-1 gene. These was also a 4-fold increase in the mRNA which hybridized with v-ki-ras probe. NIH/3T3 cells transfected with DNA from these cell lines showed transformed foci and produced tumors in nude mice. An amplified c-fos and its enhanced expression was noted for a choriocarcinoma cell line, and an increased production of mRNA for c-fos and c-N-ras was noted for a human hepatoma cell line. 2) Roles of mos and other ocogene expression in the anchorage-independent growth of S+L-mink cells superinfected with a novel murine retrovirus exhibiting dual-tropic (B- and xenotropic) properties. Marked amplification and increased expression of mos appear to correlate with the anchorage-independent growth of the superinfected S+L- mink cells. 3) Regulation of retroviral replication in murine trophoblasic tumor cells. The non-permissiveness of trophoblast cells was found to be dominant in the hybrid cells formed by fusion with a cell line permissive for retrovirsus replication. 4) Screening for monoclonal antibodies and human antibodies against HTLV. Hybridomas have been screened and some positive ones were obtained. A sero-epidemiologic survey for human anti-HTLV antibodies has been completed. 5) Permissiveness of nonlymphoid cells to HTLV-I. Some cell lines produce syncytial cells after HTLV-I infection, but the HTLV genome could not be shown to be present after months of in vitro culture.
