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.
Capillary liquid chromatography/microelectrospray-mass spectrometry (capillary LC/muESI-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/muESI-MS method provided the means for quantifying 17.5 fmol of dG-C8-IQ (2.0 adducts in 10(8) nucleosides) (S/N 10) in 300 microg 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/muESI-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 10(8) nucleosides in vivo makes this method well suited for use in future studies relating carcinogen exposure to risk in humans.
Soglia
J R
JR
Barnett Institute and Department of Chemistry, Northeastern University, Boston, Massachusetts 02115, USA.
Turesky
R J
RJ
Paehler
A
A
Vouros
P
P
D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D018736:DNA Adducts / Q000032:analysis*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000737:chemistry*; D008297:Male; D011804:Quinolines / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
D018736:DNA Adducts; D011804:Quinolines; C056105:N-(deoxyguanosin-8-yl)-2-amino-3-methylimidazolo(4,5-f)quinoline; D003849:Deoxyguanosine