title: Conversion of herpetic lesions to malignancy by ultraviolet exposure and promoter application.
abstract: 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.
mesh_terms: 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
chemical_list: D000914:Antibodies, Viral; D013755:Tetradecanoylphorbol Acetate