Tumorigenicity of Simian Papovavirus SV40 and of Virus-Transformed Cells

Summary

The tumorigenicity of the simian papovavirus SV40 and of virus-transformed cells was investigated in hamsters. A genetically purified stock of the virus readily produced tumors in newborn hamsters, and the virus could be recovered from most tumors. About half the animals developed antibodies against the virus; those failing to make antibodies did not become tolerant to a later challenge of the virus. Virus-free tumors were transplanted serially in hamsters, but no virus could be recovered from the transplanted tumors. The recipient animals did not produce SV40 antibody when tested 2 to 3 months after the tumors appeared. SV40 virus transformed human fibroblast cultures derived from embryonic lung. Cells changed from fibroblastic to epithelioid. SV40 was produced by the infected lung fibroblasts, but the virus yield declined when the cells became epithelioid. The transformed cells failed to produce tumors when inoculated in the hamster cheek pouch. Transformation in vitro of hamster embryo cells was produced by SV40. The transformed cells produced tumors when inoculated in hamsters by various routes. No virus was recovered from these cells or from the tumors produced by them. The transformed cells produced soft, highly cellular, rapidly growing tumors. Metastases were found in tumor-bearing animals. The primary hamster tumors produced by inoculation of SV40 in newborn hamsters were hard, less cellular, and slow growing; no metastases were observed. The cells from the two types of tumors were similar, appearing as a pleomorphic undifferentiated sarcoma. The chief difference was in the cellularity of the tumors, the virus-induced primary neoplasm being less cellular than the one produced by the hamster embryo cells transformed in vitro. The cells from these tumors when grown in tissue culture and the transformed cells maintained for long periods in culture had the same appearance.