Abstract
Human exposure to alkylating agents metabolized from tobacco- and food-borne carcinogens occurs regularly. Dietary inorganic compounds such as selenium and vanadium have been shown previously to provide chemoprotective benefits in rat and human trials. Here, we present biochemical data on the ability of inorganic compounds to protect DNA from alkylation damage. 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., Na2SeO4 or Na3VO4) did inhibit alkylation. We propose that these oxo species behave as nucleophilic targets for the electrophilic alkylating agents, thereby preventing DNA damage.
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Acknowledgements
We would like to thank Kevin Kelley (New England Biolabs) for his insightful discussions. This work was funded through the generosity of the Cancer Research and Prevention Foundation. Additional support was provided to J.J.W. by an Alfred P. Sloan Foundation Research Fellowship.
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Hamilton, E.E., Wilker, J.J. Inhibition of DNA alkylation damage with inorganic salts. J Biol Inorg Chem 9, 894–902 (2004). https://doi.org/10.1007/s00775-004-0597-1
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DOI: https://doi.org/10.1007/s00775-004-0597-1