Quantification of aristolochic acid-derived DNA adducts in rat kidney and liver by using liquid chromatography–electrospray ionization mass spectrometry》.pdf

Mutation Research 646 (2008) 17–24 Contents lists available at ScienceDirect Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis j o u rn al h omepage: w w w. elsev /locate/molmut C o m m u n ity add ress: w w w. elsev /locate/mutres Quantification of aristolochic acid-derived DNA adducts in rat kidney and liver by using liquid chromatography–electrospray ionization mass spectrometry Wan Chan a , Hao Yue a , Wing Tat Poon b , Yan-Wo Chan b , Oliver J. Schmitz c , Daniel W.J. Kwong a , Ricky N.S. Wong d , Zongwei Cai a,∗ a Department of Chemistry, Hong Kong Baptist University, Hong Kong, China b Hospital Authority Toxicology Reference Laboratory, Princess Margaret Hospital, Hong Kong, China c Department of Analytical Chemistry, University of Wuppertal, Germany d Department of Biology, Hong Kong Baptist University, Hong Kong, China a r t i c l e i n f o a b s t r a c t Article history: Aristolochic acid (AA), derived from the herbal genus Aristolochia and Asarum , has recently been shown to Received 8 April 2008 be associated with the development of nephropathy. Upon enzyme activation, AA is metabolized to the Received in revised form 6 August 2008 aristolactam-nitrenium ion intermediate, which reacts with the exocyclic amino group of the DNA bases Accepted 26 August 2008 via an electrophilic attack at its C7 position, leading to the formation of the corresponding DNA adducts. Available online 4 September 2008 The