Quantitation of benzo[a]pyrene-DNA adducts by postlabeling with 14C-acetic anhydride and accelerator mass spectrometry

Liquid chromatography-electrospray ionization-mass spectrometry: the future of DNA adduct detection

“…The main limitation of the technique is that it depends on the presence of an isotope such as 14 C or 3 H in the molecule of interest, which means that at present its application is restricted to experimental systems where labelled compounds may be used. However attempts have been made to develop 14 C-postlabelling procedures, which would allow the use of unlabelled carcinogens (69,70) Before the advent of LC-MS the main MS method available (and one which is still being used today) for studying DNA adducts was gas chromatography-mass spectrometry (GC-MS) utilizing electron ionization (impact) or chemical ionization (71,72). However GC-MS has been more extensively used for the determination of protein adducts, which act as surrogate markers of exposure to carcinogens (42,73,74).…”

Ultra-performance liquid chromatography–tandem mass spectrometry for rapid and highly sensitive analysis of stereoisomers of benzo[a]pyrene diol epoxide–DNA adducts

“…A number of methods have been developed for detection of BPDE-DNA adducts, including capillary electrophoresis (CE)-laserinduced fluorescence (LIF) [13][14][15][16], accelerator mass spectrometry [17,18], liquid chromatography or capillary electrophoresis-mass spectrometry [19][20][21][22][23][24][25][26], and 32 P-postlabelling [27]. However, only few methods demonstrate the capability of resolving the stereoisomers of BPDE-DNA adducts.…”

Applications of accelerator mass spectrometry for pharmacological and toxicological research

“…Recently, methods have been developed to measure adducts that resulted from an exposure in experimental systems to benzo[a]pyrene diolepoxide (Goldman et al, 2000) or to O 6 -methyldeoxyguanosine (Corcoran et al, 2004). Both studies describe the isolation of the specific adduct of interest from DNA by enzymic digestion and chromatography, followed by an optimized reaction of the nucleoside adduct with [ (Fig.…”

“…In a separate in vitro study, the putative active metabolite, benzo[a]pyrene diolepoxide, was reacted with DNA. One major adduct, 7R,8S,9R-trihydroxy-10S-(N 2 -deoxyguanosyl)-7,8,9,10-tetrahydrobenzo[a]pyrene (BPdG) was formed (Goldman et al, 2000). This structure was postlabeled with acetic anhydride to produce the major product in yields >60%.…”