Quantification of the Heterocyclic Aromatic Amine DNA Adduct N-(Deoxyguanosin-8-yl)-2-amino-3-methylimidazo[4,5-f]quinoline in Livers of Rats Using Capillary Liquid Chromatography/Microelectrospray Mass Spectrometry: A Dose−Response Study

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Abstract
Capillary liquid chromatography/microelectrospray-mass spectrometry (capillary LC/μESI-MS) was used to quantify DNA adducts of the heterocyclic aromatic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in livers of male Fischer-344 rats. Animals received a single oral dose of either 0.05, 0.50, 1.0, or 10 mg/kg IQ and were sacrificed 24 h following treatment. The major lesion identified at all doses was N-(deoxyguanosine-8-yl)-2-amino-3-methylimidazo[4,5-f]quinoline (dG-C8−IQ). The capillary LC/μESI-MS method provided the means for quantifying 17.5 fmol of dG-C8−IQ (2.0 adducts in 108 nucleosides) (S/N 10) in 300 μg of liver DNA with an intra- and interday precision of 3.5 and 6.6% (RSD), respectively. dG-C8−IQ was quantified with a mean intra- and interday accuracy of 105 ± 26 and 106 ± 28 (SD) based on back-calculated adduct masses from five standard curves analyzed over a four-week period. This is the first report on development of a capillary LC/μESI-MS method to quantify dG-C8−IQ adducts in liver DNA of rats following dosing with IQ at different levels. Furthermore, the ability to accurately and precisely quantify dG-C8−IQ at a level of 2.0 adducts in 108 nucleosides in vivo makes this method well suited for use in future studies relating carcinogen exposure to risk in humans.