Synthesis and electrospray mass spectrometric analysis of aristolochic acid Ⅰ-DNA adduct / 基础医学与临床

ABSTRACT

Objective To synthesize aristolochic acid Ⅰ(AAⅠ)-DNA adduct in vitro and to develop a method for the characterization of the adduct. Methods Aristolochic acid (AA) was incubated with 2′-Deoxyadenosine 5′-monophosphate in vitro using either enzymatic activation (by xanthine oxidase) or chemical activation (by zinc) to synthesize AAⅠ-DNA adduct. The AAⅠ-DNA adduct was characterized by the liquid chromatography electrospray ionization/tandem mass spectrometry (LC-ESI-MS/MS). Results AAⅠ-DNA adduct was prepared by two activation methods. Full scan spectra were obtained in the negative ion mode and the quasi-molecular ion peak was m/z 621. Analysis by electrospray ionization/tandem mass spectrometry (ESI-MS/MS) provided useful structural information about AAⅠ-DNA adduct. Conclusion AAⅠ can bind covalently to the exocyclic amino group of purine nucleotides to form AAⅠ-DNA adduct. LC/MS/MS is a practical tool to detect AAⅠ-DNA adduct.