#B159 Prevention of Nitric Oxide Donor Induced Carcinogenesis by Natural Source Compounds and Evaluation of the Role of Map Kinase Signaling Pathway. Harukuni Tokuda,1 Masashi Kuchide,1 Takao Konoshima,2 Midori Takasaki,1 Teruo Mukainaka,1 Wataru Aoi,1 Fumio Enjo,1 Shin-ichi Ueda,3 Ayako Kumagai,3 Hoyoku Nishino.1 Kyoto Prefectural Univ. of Medicine,1 Kyoto, Japan, Kyoto Pharmaceutical University,2 Kyoto, Japan, Kansai University,3 Suita-shi, Japan. The present study was carried out to examine the chemopreventive activity of natural source compounds, tochopherol its derivative, polyphenols, processed grain food and curcumin etc.on the nitric oxide(NO) donors induced carcinogenesis. These experiments also were to demonstrate that exposing the skin of SENCAR mice to natural source compounds prior and during peroxynitrite(PN) treatment inhibits selected intermediate pathway signaling in the PN-induced mouse skin complete carcinogenesis model, using Western blotting assay. On the fundamental findings, recent studies have suggested that these compounds were observed the inhibitory effect against PN induced tumor initiating activity using two-stage mouse skin model. Female SENCAR mouse (6 weeks of age) were treated topically with single dose of PN solution, followed by TPA twice a weekly for 20 weeks. Tumor incidence were 100% with 5 to 6 per mouse at end of experiment as positive control group. Natural source compounds were orally fed with drinking water for only 2 weeks, before and after initiation and following promoting treatment with drinking water only, as test compounds. In our observation, natural source compounds treated group cause about 60-70 % reduction in the average number of tumors per mouse after 20 weeks of experiment, respectively. Western blotting analysis of qualified epidermal particle protein showed that H-Ras,MEK and p38 expression in mouse skin were abnormal responsible for PN treatment in a time- and dose-dependent manner. Topical administration of natural source compounds had much influence against PN induced expression stage. We postulate that these data suggest possible role of Ras signaling pathway as a regulatory mechanism of chemopreventive activity in PN induced carcinogenesis. Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.