Characterization of endogenous DNA adducts by liquid chromatography/electrospray ionization tandem mass spectrometry

Abstract

Endogenous carcinogens arising from normal metabolism are known to cause modifications to DNA by reacting with bases to form adducts. Malondialdehyde is a well characterized endogenous carcinogen that forms an adduct with 2'-deoxyguanosine. This adduct has been detected in rat and human liver DNA by gas cbromatographylelectron capture negative-ion chemical ionization mass spectrometry. A method has been developed based on liquid chromatography/electrospray ionization tandem mass spectrometry for the characterization of endogenous DNA adducts. Using this method, it was unequivocally establisbed that the malondialdebyde adduct of 2'-deoxyguanosine was a constituent of human liver DNA. The methodology that has been developed should be applicable to the cbaracterization of other endogenous DNA adducts. There are few structural or biological data available to assess the importance of endogenous DNA adducts as premutagenic lesions responsible for the development of cancer. The availability of methodology based on liquid chromatograpby/electrrospray ionization tandem mass spectrometry for the characterization of DNA adducts should greatly facilitate future studies in this area.

Mutagenicity in Escherichia coli of the major DNA adduct derived from the endogenous mutagen malondialdehyde

“…M 1 G appears to be the most abundant endogenous exocyclic adduct in humans, and the structure of the material detected in human liver and white blood cells has been verified by mass spectrometry (14,19). M 1 G is the major adduct generated by reaction of malondialdehyde (MDA) with deoxyguanosine residues in DNA.…”

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

“…Rindgen et al used CNL to confirm the presence of the major C-8 adduct and two previously unidentified minor PhIP modified 2 0 -deoxyguanosine adducts detected by 32 P-postlabelling in calf thymus DNA that had been treated with N-acetoxy-PhIP in vitro (35). Chaudhary et al used solid phase extraction in conjunction with LC-ESI-MS/MS CNL to study calf thymus that had been treated with malondialdehyde as well as to confirm unequivocally the presence of the malonaldehyde-2 0 -deoxyguanosine adduct in healthy human liver DNA (141).…”

Liquid chromatography—tandem mass spectrometry analysis of the DNA adducts of aristolochic acids

“…The technique has been expanded to DNA adduct analysis since 1995 when Chaudhary et al published the first LC-ESI-MS method for nucleoside analysis [30]. Soft ionization techniques-such as electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI), combined with tandem mass spectrometry-have provided high specificity and low detection limits ranging from femto-to picomoles of DNA adducts [20 -22, 31, 32].…”