Induction of lymphomas and fibrosarcomas in nude mice after implantation of simian virus 40-transformed human meningioma.

Human cells transformed by Simian virus 40 (SV40) usually show little or no tumor formation after implantation in nude mice. In long-term studies, however, we have observed that 127 to 366 days after subcutaneous injection of SV40-transformed human meningioma cells (KJ-M2-T) into nude mice (Nu/Cox), 6 of 15 animals developed lymphomas or fibrosarcomas, usually at the site of inoculation. The induced tumors were of murine origin and were positive for SV40-T antigen. Chromosome analysis and G11 staining revealed no evidence of hybridization between human and mouse cells. No spontaneous shedding of SV40 was noted with KJ-M2-T cells in vitro; however, SV40 could be rescued after fusion of KJ-M2-T with BS-C-1 monkey kidney cells, but not with L929 mouse fibroblasts. A parallel study using SV40-transformed human fetal brain cells failed to induce tumors in nude mice despite the demonstration that infectious SV40 could also be rescued from this line after fusion with BS-C-1 but not with L-929. Subcutaneous injection of 5 X 10(3) TCID's of SV40 (strain J436) into nude mice resulted in the induction of fibrosarcomas at the injection site in 6 of 15 mice after 273 to 396 days. The induction of malignant lymphomas after implantation of SV40 transformed cells contrasted with the development of fibrosarcomas after injection of free virus. This study suggests that after subcutaneous implantation into nude mice, some SV40-transformed human tumor cell lines can serve as vectors for transmitting SV40 to murine cells causing transformation and tumor development in the host animal.