Determination of in vitro- and in vivo-formed DNA adducts of 2-amino-3-methylimidazo[4,5-f]quinoline by capillary liquid chromatography/microelectrospray mass spectrometry
Et. Gangl et al., Determination of in vitro- and in vivo-formed DNA adducts of 2-amino-3-methylimidazo[4,5-f]quinoline by capillary liquid chromatography/microelectrospray mass spectrometry, CHEM RES T, 12(10), 1999, pp. 1019-1027
Capillary liquid chromatography/microelectrospray mass spectrometry has bee
n applied to the detection of deoxyribonucleoside adducts of the food-deriv
ed mutagen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)from in vitro and in
vivo sources. Constant neutral loss (CNL) and selective reaction monitorin
g (SRM) techniques with a triple-quadrupole mass spectrometer enabled sensi
tive and specific detection of IQ adducts in vitro and in animals. Detectio
n of 1 adduct in 10(4) unmodified bases is achieved using CNL scanning dete
ction, while the lower detection limits using SRM approach 1 adduct in 10(7
) unmodified bases using 300 mu g of DNA. The DNA adducts N-(deoxyguanosin-
8-yl)-2-amino-3-methylimidazo[4,5-f]quinoline (dG-C8-IQ) and 5-(deoxyguanos
in-N-2-yl)-2-amino-3-methylimidazo[4,5-f]quinoline (dG-N-2-IQ) were detecte
d in kidney tissues of chronically treated cynomolgus monkeys at levels and
in proportions consistent with previously published P-32-postlabeling data
[Turesky, R. J., et al. (1996) Chem. Res, Toxicol. 9, 403-408]. Thus, capi
llary tandem LC/MS is a highly sensitive technique, which can be used to sc
reen for DNA adducts in vivo.