NEOPLASTIC TRANSFORMATION OF RAT EMBRYO CELLS WITH HERPES-SIMPLEX VIRUS

Sprague Dawley rat embryo cells (REF) were transformed by inoculation with herpes simplex virus (HSV) and incubation at 42.degree. C for 8 days. The infected cultures were subsequently returned to 37.degree. C and 2 types of cell clones were isolated from foci of growing cells after 4 wk. One of the clones consisted of epithelial-like cells and did not produce HSV (REF-Tep-NP). The 2nd consisted of spindle shaped cells and cultures of these cells persistently developed small areas of degeneration where production of infectious HSV (RET-Tsp-P) took place. An additional clone which did not produce any more HSV (REF-Tsp-NP) was isolated from REF-Tsp-P in the presence of HSV-antiserum. REF-Tsp-P and REF-Tsp-NP grew more rapidly than REF and also formed foci in soft agar. REF-Tep-NP had a growth rate between that of normal rat embryo cells and that of REF-Tsp-NP and REF-Tsp-P, and did not form foci in soft agar. REF-Tsp-NP cells, in contrast to REF-Tep-NP cells, were resistant to superinfection with HSV types 1 and 2. REF-Tsp-P and REF-Tsp-NP produced metastasizing sarcomas in rats. After inoculation of 103 REF-Tsp-NP cells into 1 day old rats, tumors developed rapidly. REF-Tep-NP cells did not induce tumors in rats. The parental REF cells produced no tumors, even when 108 cells were inoculated into the rats. Positive immunofluorescence was observed in all 2 transformed cells only with the hyperimmune rabbit sera but not with human anti-HSV reconvalescence immune sera.