Carcinogen interception: An investigation of the ability of inorganic oxo anions to react with alkylating agents

Elizabeth E Hamilton, Purdue University


Nitrosamines and polycyclic aromatic hydrocarbons, commonly found in cooked foods and tobacco smoke, are metabolized into potent alkylating agents. These toxins alkylate DNA leading to base mispairing, mutations, and cancer. Dietary inorganic compounds such as selenium and vanadium have been shown to prevent cancer in rat and human trials. The aqueous chemistries of selenium and vanadium are dominated by oxo anions such as (SeO4) 2- and (H2VO4)-. We propose that such oxo species may behave as nucleophilic targets for the electrophilic alkylating agents, thereby preventing DNA damage. Biochemical data on the ability of inorganic compounds to protect DNA from alkylation damage are presented. An enzyme cleavage assay is used to observe alkylated DNA. Simple salts (e.g., NaCl or NiCl2) did not prevent DNA alkylation, whereas anionic oxo species (e.g., Na2SeO 4 or Na3VO4) did inhibit alkylation. These results are consistent with our hypothesis that oxo anions may be sufficiently nucleophilic to react directly with alkylating agents thus preventing DNA alkylation. In order to understand potential interactions between oxo species and alkylating toxins, a series of ethylating agents was reacted with varied classes of oxo compounds (i.e., vanadate, selenate, phosphate, sulfate, acetate, nitrate, and nitrite). Two new organic-soluble salts, [(C4H 9)4N]3(V3O9)·0.5H 2O and [(C6H5)4P]3(O 3SeOCH2OSeO3)-(HSeO4), were synthesized and characterized for these studies. Vanadates were found to convert ethylating agents into ethanol, whereas other anions formed esters upon alkylation. General trends show that oxo anions of the greatest charge density were the most reactive. These studies suggest that the design of new compounds for cancer prevention should incorporate reactive oxo groups with high anionic charge density.




Wilker, Purdue University.

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