Alkylation of DNA by primary diazonium ions: Determination of the basis for atom site selectivity

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Xuefang Lu, lxuefan1@umbc.edu and James C. Fishbein, jfishbei@umbc.edu. Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250
Many nitrosamines are powerful carcinogens. Their biological activity is due to the formation of á-hydroxynitrosamines through metabolic activation. The á-hydroxynitrosamines decompose to form diazonium ions which can alkylate DNA. Compared to other classical alkylating agents, simple diazonium ions alkylate DNA with enhanced selectivity toward the oxygen atoms of nucleobases. The resulting oxygen adducts have been shown to give rise to mutations with high frequency. Therefore, it is of great importance to understand the factors that account for the preference of diazonium ions for oxygen atoms of nucleobases. This work was carried out to examine a recently-devised model concerning the factors that dictate atom site selectivity in the alkylation of DNA by 1-propanediazonium ion1. Reference: 1. Lu, X.; Heilman, J. M.; Blans, P.; and Fishbein, J. C. The structure of DNA dictates purine atom site selectivity in alkylation by primary diazonium ions. Chem. Res. Toxicol. 2005, 18, 1462