Joint Action of Herpes Simplex Virus and 3-Methylcholanthrene in Production of Papillomas in Mice2

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Abstract
Intradermal inoculation of herpes simplex virus into mice during a 5-day period of 3-methylcholanthrene applications to the same skin area caused faster appearance and higher incidence of skin papillomas than the chemical alone. The magnitude of this difference varied directly with the amount of infective virus in the inoculum. Tests of skin for presence of infective virus at various intervals after inoculation indicated that the virus propagated in skin. Injection of non infective control preparations had little or no effect on papilloma development. Herpes virus alone never caused papillomas. When virus was inoculated 7 days before or 14 days after the first methylcholanthrene application, the incidence of papillomas did not increase significantly. Papillomas occurred only within the methylcholanthrene-treated area and were more frequent at the site of virus injection than at the periphery. These observations indicate that the increase in papilloma incidence occurred when herpes virus propagation coincided in time and place with the epidermal hyperplasia caused by the chemical, and that the virus by itself did not act as either an inducer or a promoter.

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