<p> Metal-oxo compounds react with alkylating agents: Toxin interception and implications for cancer prevention.</p><p>Jessica M. Fautch, Sarah M. Gentry, Elizabeth E. Hamilton, and Jonathan J. Wilker*</p><p>Department of Chemistry, Purdue University, West Lafayette, IN 47907-2084</p><p>Toxins found in cooked foods and tobacco smoke, such as nitrosamines and polycyclic aromatic hydrocarbons, metabolize into potent alkylating agents and subsequently react with nucleophilic positions on DNA. Human diets also contain inorganic compounds, many of which form anionic oxo species in water. Numerous studies report decreased incidences of cancer when diets are supplemented with inorganics such as selenium1 and vanadium2,3 salts. We are exploring a potential mechanism of cancer prevention in which these inorganic species may be nucleophilic, thereby reacting directly with the electrophilic alkylating toxins. By consuming the alkylating toxin prior to reaction with DNA, formation of mutagenic lesions could be prevented. Results from our lab show that vanadium and selenium oxo compounds prevent DNA damage, while producing relatively harmless alcohols as a product. However, metal-oxo compounds may mimic phosphate and thus have toxicity and cellular uptake difficulties. Also, because metal-oxo compounds equilibrate to several species in a physiological environment, their reactivity is difficult to control. These issues led us to examine the interactions of vanadium-oxo ligand compounds with alkylating agents. Dioxovanadium(V) salicylidenehydrazide, [VO2(salhyph)]K, and its derivatives have been examined in detail. Specifically, changing the electron-donating or electron-withdrawing ability of the ligand provides an array of compounds with diverse reactivity. We are reacting this family of compounds with alkylating toxins, characterizing the products, and examining kinetics of these reactions.</p><p>1 Finley, J. W.; Clement, I.; Lisk, D. J.; Davis, C. D.; Hintze, K. J.; Whanger, P. D. J. Agric. Food Chem. 2001, 49, 2679-2683. 2 Thompson, H. J.; Chasteen, N. D.; Meeker, L. D. Carcinogenesis 1984, 5, 849-851. 3 Bishayee, A.; Chatterjee, M. British J. Cancer 1995, 71, 1214-1220.</p>