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

J. R. Soglia, R. J. Turesky, A. Paehler, P. Vouros

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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.

Original languageEnglish (US)
Pages (from-to)2819-2827
Number of pages9
JournalAnalytical chemistry
Volume73
Issue number13
DOIs
StatePublished - Jul 1 2001

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