? ? Cancers of the oral cavity account for 2.5% of cancers in the United States and are the sixth most common cancer worldwide with a five year survival of approximately 50%; the number of deaths per year has not significantly changed in the past 3 decades. Because of this high mortality rate and since present treatments are relatively ineffective, intervention methods for oral cancer must be developed and tested in animal models. An animal model of oral cancer, the hamster cheek pouch (HCP), has shown that cell and tissue changes that are involved in the cancer process are similar between humans and hamsters. Because of these similarities, we have used the hamster oral cancer model to demonstrate chemopreventive activity of black raspberries and have translated this research into Phase Ib-IIa human clinical trials. The current application expands an ongoing project funded by the California Strawberry Commission in which lyophilized strawberries (LS) are being used to inhibit formation and development of oral cancers. In the current proposal, we will evaluate the combined effect of LS and selenium on the chemoprevention of oral cancer using strawberries that have selenium incorporated during formation of the fruit. Three different protocols will be used. In the first, hamsters will be given a diet of AIN-76A pellets containing 0% or 10% powdered LS or LS-selenium (LS-Se) beginning one week prior to treatment of the HCP with a chemical carcinogen (3X/wk for 8 wks); LS and LS-Se feeding is continued through 13 wks (Complete Chemoprevention Protocol). In the second and third, HCP will be initiated with chemical carcinogen (3X/wk for 6-7 wks) and beginning 48 hrs after the last dose of carcinogen, hamsters are given a diet of AIN-76A pellets containing 0% or 10% LS or LS-Se or treated topically 3x/week with 0% or 10% LS or LS-Se (Post-initiation Protocols). Control animals receive only AIN- 76A pellets or solvent vehicle. The Post-initiation experiments will mimic a condition similar to that seen in former tobacco users. We anticipate that the strawberry powder will inhibit tumor formation when given in the diet before, during, or after carcinogen treatment, as we have observed with black raspberries. Further, based on studies showing chemopreventive activity of selenium alone, we posit that treatment with LS-Se will result in a significant enhancement of chemopreventive activity and will inhibit progression of dysplastic lesions into overt tumors. A successful outcome of the post-initiation experiments will lead to human clinical trials in high risk populations using LS or LS-Se in a vehicle compatible with human consumption. ? ? ?
