Abstract Number: 5670 Prevention of chemical carcinogen-induced oxidative DNA damage, Ha-ras mutation and epidermal hyperplasia in the mouse skin by natural source antioxidants Erick Spears, Effat Kordari, Margaret Hanausek, Zbigniew Walaszek, Thomas J. Slaga, AMC Cancer Research Center, Denver, CO. The primary goal of this study was to demonstrate that exposing the skin of SENCAR mice to natural source and synthetic antioxidants prior to and during 7,12-dimethylbenz[a]anthracene (DMBA) treatment inhibits selected intermediate end-point biomarkers in the DMBA-induced mouse skin complete carcinogenesis model, i.e., the 4-week inflammatory-hyperplasia assay. The antioxidants were administered either topically or orally. Another goal of the present study was to show that combined topical and dietary administration of selected antioxidants, prior to and during DMBA treatment, inhibits synergistically intermediate end-point biomarkers such as DMBA-induced epidermal hyperplasia and DNA oxidative damage (anti-tumor-promotion) or Ha-ras mutations (anti-initiation). The antioxidants used in this study include the natural source antioxidants: grape seed extract, pycnogenol, green tea extract, coenzyme Q10, and lutein as well as α-tocopherol and L-ascorbic acid as the control antioxidants. Topical application of the grape seed extract, pycnogenol, green tea extract, coenzyme Q10 and lutein strongly and in a dose-related manner inhibited DMBA-induced epidermal hyperplasia in a standard in vivo mouse model of complete skin carcinogenesis. Also, the dietary administration of the above mentioned antioxidants markedly and in a dose-related manner inhibited DMBA-induced epidermal hyperplasia in the same model of skin carcinogenesis. DMBA-mediated epidermal hyperplasia, oxidative DNA damage, i.e., hydroxylation of 2¢-deoxyguanosine, and the occurrence of DMBA-mediated Ha-ras mutations were reduced synergistically with the topical/dietary regimen of antioxidants. In conclusion, combination treatments (i.e., dietary and topical) with two different antioxidants or the same antioxidant give better results than dietary or topical treatments alone. In selecting natural source antioxidants for future chemopreventive studies, the antioxidants or their combinations with the broad spectrum of antioxidant activities should be taken into account, i.e., those that are able effectively quench peroxyl and hydroxyl radicals as well as superoxide anions and other free oxygen radicals. 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.