Cancer of the mouth is probably the result of the interaction of several factors. Epidemiological studies have shown that the disease is more common in cigarette smokers, and the risk increases with an increase in the amount smoked per day. Smokers have higher levels of antibody to Herpes simplex virus type-1 (HSV-1) than non-smokers, and antibody to HSV-1 is associated with oral cancer. We will use and animal model to test the hypothesis that constituents of cigarette smoke can reactivate latent herpes simplex virus, and that a co-carcinogenic interaction between them causes the tumor. Mice will infected on the skin with an oral isolate HSV-1. After the infection has resolved and the virus has become latent, experiments will show if it can be reactivated with condensates of tobacco smoke and with various polycyclic hydrocarbons. If HSV is found to increase the rate of the tumor induction, the role of the virus will be studied to find if it is an initiator, a promotor, or both. The tumors will be examined for HSV antigens by a peroxidase-antiperoxidase method. The mice's serum antibodies to HSV will be measured by an enzyme-linked immunosorbent assay, and HSV DNA will be sought in the tumor cells by nucleic acid hybridization. Efforts will then be made to inhibit the co-carcinogenic effect with selected drugs. Data obtained will be compared with existing data from human patients to find if the animal model is comparable with the human disease. This project will accumulate evidence to support or refute a possible etiology of oral cancer, and it may provide a rational mechanism for the prevention of that disease.
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