TY - JOUR
T1 - Liquid Chromatography-Tandem Mass Spectrometry Analysis of the DNA Adducts of Aristolochic Acids
AU - Chan, Wan
AU - Zheng, Yufang
AU - CAI, Zongwei
N1 - Funding Information:
The authors thank the Faculty Research Grant of the Hong Kong Baptist University (FRG/04-05/II-35) and the Research Grant Council, University Grants Committee of Hong Kong (HKBU2459/06M) for the financial support of this study.
PY - 2007/4
Y1 - 2007/4
N2 - Electrophilic attack of aristolactam-nitrenium ion by the C7 position to the exocyclic amino group in the DNA bases led to the formation of the major adducts. In this study, liquid chromatography coupled with electrospray ionization tandem mass spectrometry was applied to the study of DNA adducts of aristolochic acid (AA). When DNA (bases and CT-DNA) was incubated with AA, dG-AAI, dG-AAII, dA-AAI, dA-AAII, dC-AAI, and dC-AAII were detected and characterized. The dC adducts of AA were identified for the first time. The soft ionization technology allowed detection of the intact DNA adducts. High-resolution MS and MS-MS capabilities of a quadrupole time-of-flight mass spectrometer were shown to be efficient for DNA adducts analysis. DNA-AA adducts showed characteristic fragmentation patterns in MS-MS analysis. The dissociative loss of 116 Da from the DNA-AA adducts, which resulted from internal hydrogen transfer and cleavage at the C{single bond}N glycosidic bond, provided a characteristic fragment for the structural elucidation.
AB - Electrophilic attack of aristolactam-nitrenium ion by the C7 position to the exocyclic amino group in the DNA bases led to the formation of the major adducts. In this study, liquid chromatography coupled with electrospray ionization tandem mass spectrometry was applied to the study of DNA adducts of aristolochic acid (AA). When DNA (bases and CT-DNA) was incubated with AA, dG-AAI, dG-AAII, dA-AAI, dA-AAII, dC-AAI, and dC-AAII were detected and characterized. The dC adducts of AA were identified for the first time. The soft ionization technology allowed detection of the intact DNA adducts. High-resolution MS and MS-MS capabilities of a quadrupole time-of-flight mass spectrometer were shown to be efficient for DNA adducts analysis. DNA-AA adducts showed characteristic fragmentation patterns in MS-MS analysis. The dissociative loss of 116 Da from the DNA-AA adducts, which resulted from internal hydrogen transfer and cleavage at the C{single bond}N glycosidic bond, provided a characteristic fragment for the structural elucidation.
UR - http://www.scopus.com/inward/record.url?scp=33947304167&partnerID=8YFLogxK
U2 - 10.1016/j.jasms.2006.11.010
DO - 10.1016/j.jasms.2006.11.010
M3 - Journal article
C2 - 17208007
AN - SCOPUS:33947304167
SN - 1044-0305
VL - 18
SP - 642
EP - 650
JO - Journal of the American Society for Mass Spectrometry
JF - Journal of the American Society for Mass Spectrometry
IS - 4
ER -