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/Microe
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- 作者：John R. Soglia ; Robert J. Turesky ; Axel Paehler ; and Paul Vouros
- 刊名：Analytical Chemistry
- 出版年：2001
- 出版时间：July 1, 2001
- 年：2001
- 卷：73
- 期：13
- 页码：2819 - 2827
- 全文大小：124K
- 年卷期：v.73,no.13(July 1, 2001)
- ISSN：1520-6882
文摘
Capillary liquid chromatography/microelectrospray-massspectrometry (capillary LC/
r.gif">ESI-MS) was used to quantifyDNA adducts of the heterocyclic aromatic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in livers of maleFischer-344 rats. Animals received a single oral dose ofeither 0.05, 0.50, 1.0, or 10 mg/kg IQ and weresacrificed 24 h following treatment. The major lesionidentified at all doses was N-(deoxyguanosine-8-yl)-2-amino-3-methylimidazo[4,5-f]quinoline (dG-C8-IQ). Thecapillary LC/r.gif">ESI-MS method provided the means forquantifying 17.5 fmol of dG-C8-IQ (2.0 adducts in 108nucleosides) (S/N 10) in 300 r.gif">g of liver DNA with anintra- 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 thefirst report on development of a capillary LC/r.gif">ESI-MSmethod to quantify dG-C8-IQ adducts in liver DNA of ratsfollowing 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 vivomakes this method well suited for use in future studiesrelating carcinogen exposure to risk in humans.
r.gif">ESI-MS) was used to quantifyDNA adducts of the heterocyclic aromatic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in livers of maleFischer-344 rats. Animals received a single oral dose ofeither 0.05, 0.50, 1.0, or 10 mg/kg IQ and weresacrificed 24 h following treatment. The major lesionidentified at all doses was N-(deoxyguanosine-8-yl)-2-amino-3-methylimidazo[4,5-f]quinoline (dG-C8-IQ). Thecapillary LC/r.gif">ESI-MS method provided the means forquantifying 17.5 fmol of dG-C8-IQ (2.0 adducts in 108nucleosides) (S/N 10) in 300 r.gif">g of liver DNA with anintra- 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 thefirst report on development of a capillary LC/r.gif">ESI-MSmethod to quantify dG-C8-IQ adducts in liver DNA of ratsfollowing 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 vivomakes this method well suited for use in future studiesrelating carcinogen exposure to risk in humans.