Efficient synthesis, liquid chromatography purification, and tandem mass spectrometric characterization of estrogen-modified DNA bases.

ABSTRACT: Estrogens are metabolized to active quinones that modify DNA and may lead to various cancers. To extend the analytical methodology for estrogen-modified purine bases, we report here a simple modification to existing synthetic procedures that use 2-iodoxybenzoic acid (IBX) as the oxidizing agent for the reference material and putative biomarker, 4-hydroxyestrone-1-N3adenine (4-OH-E1-1-N3Ade). The reaction leads to two catechol estrogen quinones, CE1-2,3-Q and CE1-3,4-Q, both of which react via Michael additions to afford 4-OH-E1-1-N3Ade and other DNA adducts. Liquid chromatography separation permits the isolation of high-purity 4-OH-E1-1-N3Ade. With this method, we also prepared single 13C and uniformly 15N (U-15N) labeled 4-OH-E1-1-N3Ade with 8-13C-labeled Ade and U-15N-labeled adenosine 5

SUBMITTER: Zhang Q 

PROVIDER: S-EPMC2656942 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature