Suppression of transformation and tumorigenicity in interspecies hybrids of human SV40-transformed and mouse 3T3 cell lines.

Somatic cell hybrids, formed by fusion of human SV40-transformed fibroblast lines and mouse 3T3 cells, were isolated and analysed for expression of transformation phenotypes and tumorigenic potential in immunodeficient nude mice. Both tumorigenic and nontumorigenic SV40-transformants were used for these experiments. Regardless of whether or not the parental human transformed parent line was tumorigenic, the hybrid progeny-with rare exception-did not form tumors. The possibility that human SV40-transformed lines and the derived hybrid progeny were immunologically rejected in nude mice was unlikely since fusion of these human lines to a tumorigenic 3T3 variant produced hybrids which were highly tumorigenic. In addition, in these hybrid lines, there was not a coordinate expression of SV40 T-antigen and transformation traits. The phenotypic separation in somatic cell hybrids of SV40 T-antigen expression and transformation phenotypes and tumorigenicity is evidence that host genetic changes, occurring during or subsequent to viral integration, also contribute to the expression of those traits in SV40-transformed cells. The general inability of human SV40-transformations to form tumors in nude mice would result from their inherent nontumorigenicity and reflect the relative rarity, compared to SV40-transformed mouse cells, of those host genetic changes determining tumorigenicity. The postulated role of an interaction between viral and cellular genetic changes was supported by other results hybrid lines formed by fusion of LNSV cells and the tumorigenic 3T3 derivative were markedly more anchorage independent than either parental line or LNSV/3T3 hybrid cells.