Conversion of herpetic lesions to malignancy by ultraviolet exposure and promoter application.
Many lines of evidence exist associating herpes simplex virus (HSV) with the development of carcinoma, but much of this evidence is anecdotal or associative in nature and does not prove a cause and effect. The purpose of this research was to investigate the oncogenic potential of HSV type 2 (HSV-2) in vivo. A mouse model for lip carcinogenesis was designed to combine HSV-2 infection, u.v. exposure and tetradecanoyl-phorbol-acetate (TPA) application. HSV-2 inoculation on to abraded mouse lips was capable of causing vesicular ulcerative lesions which healed completely after 10 to 14 days. Ultraviolet irradiation of the HSV lesion site daily for 6 min at 42 ergs/mm2/s on days 3 to 6 post-infection caused hyperkeratosis, acanthosis and dysplasia to develop in several lips; while the same u.v. exposure by itself failed to alter the histologic appearance. The addition to repeated TPA application to the HSV+ u.v. regimen promoted tumour emergence. Thirty-two of 156 Balb/c mice developed tumours. Although the majority were papillomas, six were squamous cell carcinomas. These tumour-bearing mice had increased HSV-specific antibody titres. HSV antigens were shown to be present in outgrowths from explanted tumours as well as in tumour biopsies by immunoperoxidase staining with HSV-specific antisera. It is suggested that the in vivo u.v.-irradiated HSV acted as the inducer and TPA as the promoter, analogous to the classical two-stage carcinogenesis model.
D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000209:etiology*; D006560:Herpes Labialis / Q000150:complications*; D008046:Lip / Q000473:pathology; D008048:Lip Neoplasms / Q000209:etiology*; D008297:Male; D051379:Mice; D009500:Neutralization Tests; D010212:Papilloma / Q000209:etiology*; D018139:Simplexvirus / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014466:Ultraviolet Rays
D000914:Antibodies, Viral; D013755:Tetradecanoylphorbol Acetate