TY - JOUR
T1 - 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
T2 - A dose - Response study
AU - Soglia, J. R.
AU - Turesky, R. J.
AU - Paehler, A.
AU - Vouros, P.
PY - 2001/7/1
Y1 - 2001/7/1
N2 - 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.
AB - 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.
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U2 - 10.1021/ac010218j
DO - 10.1021/ac010218j
M3 - Article
C2 - 11467522
AN - SCOPUS:0035387450
VL - 73
SP - 2819
EP - 2827
JO - Industrial And Engineering Chemistry Analytical Edition
JF - Industrial And Engineering Chemistry Analytical Edition
SN - 0003-2700
IS - 13
ER -