摘要：

This chapter summarizes work in signal transduction pathways involved in neoplastic cell transformation and carcinogenesis, and presents strong evidence for these pathways as effective targets for chemopreventive agents. The study of the molecular mechanisms of cancer development and the action of anticancer agents in cancer prevention is discussed in this chapter. It address fundamental questions concerning the response of animal and/or human cells to carcinogens and tumor promoters, such as UV light, arsenic, TPA, and growth factors and established a series of necessary models or systems, such as the over-agar assay for cell transformation , gene knockout mice, transcription factor/luciferase promoter stably transfected cells and transgenic mice, as well as gene knockdown (siRNA) or dominant-negative mutant stably transfected cell lines. These models have been extensively utilized to examine the tumor promoter-induced signal transduction pathways and their role in cell neoplastic transformation. The chapter discusses the signal transduction networks induced by UVA, UVB and UVC, and describes the critical roles of MAP kinases at all three unique wavelengths of UV-induced signal transduction pathways. Some of the most interesting and well documented are resveratrol and components of tea, EGCG, theaflavins, and caffeine. Other potentially effective dietary compounds include inositol hexaphosphate, PEITC, ginger, and CAPE. A continuing emphasis on obtaining rigorous research data and critical analysis of those data regarding these and other food factors is vital to determine the molecular basis and long-term effectiveness and safety of these compounds as chemopreventive agents. Large-scale animal and molecular biology studies are needed to address the bioavailability, toxicity, molecular target, signal transduction pathways, and side effects of dietary factors. Clinical trials based on clear mechanistic studies are also needed to assess the effectiveness of these dietary factors in the human population.

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