Abstract
Adult male Syrian hamsters were inoculated subcutaneously with herpes simplex virus type 1 (HSV-1, 106 PFU) or ultraviolet-inactivated HSV-1. One week later 12-O-tetradecanoylphorbol 13-acetate (TPA, 2×20 nmol weekly) was topically applied to the dorsal skin at the site of virus inoculation for 6 months. Control animals received HSV-1 only or topical treatment with TPA in acetone or acetone alone. Small tumour nodules developed in the HSV-1 group close to the site of virus inoculation 10–15 months after the beginning of the experiment. The neoplasms were classified as angiolipomas, chondromyxomas, a hibernoma, and an unclassified tumor resembling a Kaposi sarcoma in humans. The topical TPA treatment alone induced melanocytic hyperplasia and sebaceous gland hyperplasia. The soft-tissue tumours differed markedly from the structure of the soft-tissue sarcomas induced in Syrian hamsters by viruses of the papova and polyoma groups. Since the spontaneous incidence of benign soft-tissue tumours in our close hamster colony is extremely low, we concluded that mutagenic HSV-1 effects on hamster mesenchymal cell DNA may be involved in the process of formation of the observed benign neoplasms.
Key words: Herpes simplex virus type 1 (HSV-1), viral carcinogenesis, 12-O-Tetradecanoylphorbol 13-acetate (TPA)
Abbreviations
- HSV-1
herpes simplex virus type 1
- TPA
12-O-tetradecanoylphorbol 13-acetate
References
- Amtmann E, Volm M, Wayss K (1984) Tumor induction in the rodentMastomys natalensis by activation of endogenous papillomavirus genomes. Nature 308:291–291 [DOI] [PubMed] [Google Scholar]
- Berman LD (1967) Comparative morphologic study of the virus induced solid tumors of Syrian hamsters. JNCI 39:847–901 [PubMed] [Google Scholar]
- Berman L, Soto E, Chesterman F (1982) Tumours of the soft tissues. IARC Sci Publ 34:293–324 [PubMed] [Google Scholar]
- Bernfeld P, Homburger F (1983) Skin painting studies in Syrian hamsters. Prog Exp Tumor Res 26:128–153 [DOI] [PubMed] [Google Scholar]
- Brown K, Quintanilla M, Ramsden M, Kerr IB, Young S, Balmain A (1986) V-ras genes from Harvey and BALB murine sarcoma viruses can act as initiators of two-stage mouse skin carcinogenesis. Cell 46:447–456 [DOI] [PubMed] [Google Scholar]
- Fisher PB, Weinstein IB (1979) Chemical-viral interactions and multistep aspects of cell transformation. IARC Sci Publ 27:113–131 [PubMed] [Google Scholar]
- Goerttler K, Loehrke H, Schweizer J, Hesse B (1980) Two-stage tumorgenesis of dermal melanocytes in the back skin of the Syrian golden hamster using systemic initiation with 7, 12-dimethylbenz(a)anthracene and topical promotion with 12-O-tetradecanoylphorbol-13-acetate. Cancer Res 40:155–161 [PubMed] [Google Scholar]
- Hausen H zur, Bornkamm GW, Schmidt R, Hecker E (1979) Tumor initiators and promoters in the induction of Epstein-Barr virus. Proc Natl Acad Sci USA 76:782–785 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hausen H zur (1982) Human genital cancer: synergism between two virus infections or synergism between a virus infection and initiating events. Lancet ii:1370–1372 [DOI] [PubMed] [Google Scholar]
- Klotz U, Hergenhahn M, Fellhauer M, Hecker E (1989) Induction of Epstein-Barr virus early antigens by tumor promoters of the diterpene ester type in Raji cells and specific (receptor) binding as compared to irritant and promoting activities. J Cancer Res Clin Oncol 115:148–156 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nahmias AJ, Naib ZM, Josey WE, Murphy FA, Luce CF (1970) Sarcomas after inoculation of newborn hamsters with herpes virus hominis type 2 strains. Soc Exp Biol Med 134:1065–1069 [DOI] [PubMed] [Google Scholar]
- Rous P, Kidd JG (1938) The carcinogenic effect of a papilloma virus on the tarred skin of rabbits. Description of the phenomenon. J Exp Med 67:399–422 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schlehofer JR, Hausen H zur (1982) Induction of mutations within the most cell genome by partially inactivated herpes simplex virus type 1. Virology 122:471–475 [DOI] [PubMed] [Google Scholar]
- Schlehofer JR, Gissmann L, Matz B, Hausen H zur (1983) Herpes simplex virus-induced amplification of SV 40. Int J Cancer 32:99–103 [DOI] [PubMed] [Google Scholar]
- Trentin JJ, Van Hoosier GL, Ferguson DB, Kitamura T (1969) Oncogenic evaluation in hamsters of human picorna-, paramyxo- and herpesviruses. Proc Soc Exp Biol Med 132:912–915 [DOI] [PubMed] [Google Scholar]
