In vitro isolation of stable rat sarcoma viruses

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Abstract
A Sprague-Dawley (SD-1) rat embryo [fibroblast] culture, at low passage level, released an endogenous ecotropic type C virus (SD-RaLV) and after about 20 further passages it underwent spontaneous transformation. The SD-RaLV, released from the transformed cells, did not cause rapid transformation of other rat embryo cells. When the transformed cells were repeatedly cocultivated with 3 different chemically transformed and serially transplanted rat tumor cell lines (sarcoma, carcinoma and hepatoma), rapidly fibroblast-transforming sarcoma viruses (RaSV) were recovered after each attempt. RaSV was not recovered from 1 of these tumor cell lines before transplantation, nor could focus-forming virus be rescued from these same tumor cells by cocultivation with other cells releasing heterologous type C viruses. Foci were induced on normal rat kidney and several other rat embryo cell strains within 7-15 days. Both productive and nonproductive NRK clones were derived. The productive clones were positive for rat specific p30 antigen and the RaSV released were serially transmitted to other rat embryo cells. RaSV genome was rescued from the nonproductive clones by superinfection with SD-RaLV, wild rat type C virus and several heterologous type C viruses. These observations appear to represent naturally occurring transformation-specific (src) genes being recovered in vitro in the form of stable sarcoma viruses. These viruses differ from the Kirsten and Harvey strains of murine sarcoma virus in that they apparently contain no MuLV sequences and are of purely rat origin.