The ultimate goal of this project is to find an agent that will cause a reversal of preneoplasia in epithelial tissue. The compounds currently being investigated are vitamin A and its analogs (retinoids). In order to better understand the effect of retinoids on the differentiation of preneoplastic epithelial tissue three major areas are being studied. (1) The biochemical mechanism of action of vitamin A in the epithelial cell. (2) The metabolism of Vitamin A with special emphasis on determining the final active form of the vitamin. (3) The search for analogs of vitamin A that display biological activity in the reversal of preneoplasia and, at the same time, show low toxicity in the animal.