TUMOR PRODUCTION BY HSV-2 TRANSFORMED LINES IN RATS AND THE VARYING RESPONSE TO IMMUNOSUPPRESSION

Rat embryo cells transformed by two ts mutants of HSV-2 strain HG 52 and also by u.v.-irradiated HSV-2 strain 333 were inoculated into highly inbred host rats, either newborn or which had undergone various immunosuppressive treatments. The latent period before a palpable tumour (a fibrosarcoma) was detected varied directly with the degree of immunosuppression of the host. Transformed cells could form tumours after a latent period of nearly 2 years. All tumours were invasive and in some cases metastatic. The continuing expression of HSV information in 10 tumour cell lines was demonstrated by perinuclear and cytoplasmic staining in immunofluorescence studies using a rat antiserum directed against the early polypeptides of HSV-2 HG 52 infection and a rabbit serum prepared against a 24 h cell infection with HSV-2 HG 52 ts 1. Sera from tumour-bearing rats fluoresced the surface of unfixed human or rat embryo cells 4 to 5 h after infection with HSV-2 HG 52. In addition the rabbit antiserum (4740 or 4741) fluoresced the surface of 80% of the tumour cells in culture. Transplanted tumours after 20 passages in vitro and taking up to a year to again form a tumour in a host rat also showed specific HSV cytoplasmic and perinuclear fluorescence in tests with the rat antiserum directed against early polypeptides of HSV-2 lytic infection.