Neoplastic transformation of rat embryo cells with herpes simplex virus

Abstract

Sprague Dawley rat embryo cells (REF) were transformed by inoculation with herpes simplex virus (HSV) and incubation at 42°C for 8 days. The infected cultures were subsequently returned to 37°C and two types of cell clone were isolated from foci of growing cells after 4 weeks. One of the clones consisted of epithelial-like cells and did not produce HSV (TEF-tep-NP). The second consisted of spindle-shaped cells and cultures of these cells persistently developed small areas of degeneration where production of infectious HSV (REF-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 both 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-P and REF-Tsp-NP produced metastasizing sarcomas in rats. After inoculation of 10³ REF-Tsp-NP cells into 1-day-old rats tumours developed rapidly. REF-Tep-NP cells did not induce tumours in rats. The parental REF cells produced no tumours, even when 10⁸ cells were inoculated into the rats. Positive immunofluorescence was observed in all three transformed cells only with the hyperimmune rabbit sera but not with human anti-HSV reconvalescence immune sera.