The inhibitory action of tea (Camellia sinenis) and tea components against carcinogenesis has been demonstrated in animal models. The overall goal of this program project is to elucidate the mechanisms of inhibition of carcinogenesis by tea and the active components involved. The common hypothesis is that tea polyphenols and caffeine, and their metabolites, inhibit carcinogenesis by suppressing cell proliferation and enhance apoptosis via modulating key signal transduction and metabolic pathways. The inhibition of AP-l related signaling pathways and arachidonic acid metabolism will receive major attention. A novel hypothesis to be tested is that tea consumption lowers body fat levels and this effect contributes to the inhibition of carcinogenesis. The themes of the three Projects are as follows: Project 1, "Effects of Tea on the Formation and Growth of Skin Tumors," will investigate the inhibition of skin carcinogenesis in UVB-induced high-risk mice by orally and topically applied tea, caffeine, and EGCG; the mechanisms of growth inhibition and apoptosis induction; and the role of "lowering body fat levels" in anticarcinogenesis. Project 2, "Inhibition of Lung Carcinogenesis and General Mechanistic Studies," will study the entailed mechanisms in vivo and in vitro (especially on the inhibition of signal transduction kinases), the biotransformation and tissue levels of tea constituents, and the biological activities of key constituents and metabolites. Project 3, "Modulation of Signal Transduction Pathways by Tea Components" will focus on mechanisms key? to the inhibition of cell transformation and apoptosis in cell lines by caffeine and polyphenols as well as their derivatives, using cell and molecular biology approaches. Facilitated by the "Tea Chemistry and Analysis Core" and "Administrative Core, "the three Projects are highly interactive and integrated. Jointly, we intend to make major contributions to the use of tea for the I chemoprevention of cancer.