Tumorigenicity of SV40-transformed human and monkey cells in immunodeficient mice

Human cells transformed in vitro by SV40 to the anchorage-independent state rarely form tumors in nude mice and therefore constitute an important exception to the otherwise tight correlation between anchorage independence and cellular tumorigenicity. In this paper we explore a number of possible explanations for this unusual situation. We find that the phenomenon is not restricted to human cells but includes monkey cells as well. The nontumorigenic phenotype of the primate SV40 transformants is highly stable. We are unable, through selection of ever more anchorage-independent lines, to generate a primate SV40 transformant which will grow as a tumor in even the most immunologically crippled animals. One tumor was obtained from SV80 (an SV40-transformed human cell line) following injection into a mouse deficient in both T and B cell functions. However, cell lines derived from this tumor are not significantly more tumorigenic than the SV80 parent. This low incidence of tumor formation is not due to the fact that the primate cells are transformed by nononcogenic defective viral genomes nor to a nutritional inadequacy of the host animal for the growth of human cells. Although a T cell-independent mechanism may be the major mechanism involved in tumor suppression, it is unlikely that this completely accounts for the general lack of tumor growth by most of these cells. It appears that the interaction of SV40 (a primate virus) with primate cells may be intrinsically less oncogenic than its interaction with rodent cells.