Environmental exposure to UV light is a major etiologic factor in the development of human skin cancers. Experimentally, UV acts both as tumor initiator and a tumor promoter in animal models. It is recognized that certain nutritional factors and phytochemicals play an important role in an individual's susceptibility to environmental carcinogens. Understanding of the underlying mechanisms will enhance the effectiveness of prevention and therapeutic efforts. Our preliminary studies indicate that apple peel extract has antioxidant activities. It inhibits ultraviolet (UVB, 280-320 nm) radiation-induced AP-1 activation both in vitro and in vivo, possibly by interfering with signal transduction events involving MAP kinase, ERKs, and JNK. Cell transformation studies show that apple peel extract inhibited TPA-induced cell transformation. We hypothesize that apple peel extract may function as an antioxidant and as a chemopreventive agent against oxidative stress-induced carcinogenesis. We will use UVB-induced skin carcinoma as a model to test this hypothesis.
Four specific aims are proposed.
Specific Aim 1 will identify the active antioxidant components of apple peel extract. We will study the antioxidant properties of various chromatographic fractions derived from apple peel extract and examine the phenolic compounds identified previously for their reaction rates toward oxygen free radicals.
Specific Aim 2 will investigate antioxidant properties of apple peel extract, individual fraction, and previously identified phenolic compounds in JB6 cells and in living animals.
Specific Aim 3 will investigate the effects of apple peel extract on UVB-induced activation of AP-1, NF-DB, and NAFT in vitro and in vivo.
Specific Aim 4 will evaluate the effects of apple peel extract, individual fraction, and previously identified phenolic compounds on UVB-induced lipid peroxidation, protein oxidation, oxidative DMA damage, and carcinogenesis in SKH-1 hairless mice exposed to UVB.
This Aim will also investigate the effects of apple peel preparations on proliferative and/or cell deletion activities by measuring proliferation and apoptosis. This application can be used as a preclinical study for nutritional intervention against cancer resulting from environmental exposure to UV light. This study is related to the priority areas of the Public Health Service program, """"""""Healthy People 2010,"""""""" which is committed to achieving the promotion of health and prevention of disease. Thus, the results may have an important impact on public health. ? ? ?
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