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Quantitative analysis of 1,3-butadiene-induced DNA adducts in vivo and in vitro using liquid chromatography electrospray ionization tandem mass spectrometry.
J Mass Spectrom. 1998 Apr; 33(4):363-76.JM

Abstract

1,3-Butadiene (BD) is a high volume industrial chemical which is known as a multi-site rodent carcinogen and is classified as a probable human carcinogen. Covalent interactions of the reactive epoxy metabolites of BD with DNA lead to the formation of DNA adducts which may cause mutations and tumor formation. In the present work, liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) was employed for analyses of BD-induced DNA adducts in vitro and in vivo. Selected reaction monitoring (SRM) using the fragmentation of the [M + H]+ ions of the adducts to the corresponding protonated nucleobases under collision-induced dissociation was performed. Quantitation was based on isotope dilution with 13C- and 15N-labeled internal standards. The methods were applied in vitro [calf thymus DNA and TK6 cell cultures treated with epoxy metabolites of BD, 3,4-epoxy-1-butene (EB) and diepoxybutane (DEB)] and in vivo [DNA isolated from tissues of BD-exposed laboratory animals]. Two regioisomers of N-7-EB-guanine adducts, N-7-(2-hydroxy-3-buten-1-yl)guanine (N-7-EB-Gua I) and N-7-(1-hydroxy-3-buten-2-yl)guanine (N-7-EB-Gua II) and two N-3-EB-adenine isomers, N-3-(2-hydroxy-3-buten-1-yl)adenine and N-3-(1-hydroxy-3-buten-2-yl)adenine (N-3-EB-Ade I and II), were found in EB-exposed samples. N-7-(2',3',4'-trihydroxybut-1'-yl)guanine (N-7-THB-Gua), N6-(2',3',4'-trihydroxybut-1'-yl)adenine (N6-THB-Ade), and N-3-(2',3',4'-trihydroxybut-1'-yl)adenine (N-3-THB-Ade) were detected in DEB-treated DNA. DNA isolated from liver and lung of rats and mice exposed to 1250 ppm BD for 2 weeks contained both regioisomers of N-7-EB-Gua and N-3-EB-Ade, as well as N-7-THB-Gua and N6-THB-Ade. The methods developed in this work provide the means to study accumulation, repair and dose-response relationships of BD-DNA adducts in vivo. Although less sensitive than gas chromatography/electron capture negative ionization high-resolution mass spectrometry (GC/ECNI-HRMS), LC/ESI(+)-MS/MS in the SRM mode is extremely useful for analysis of BD-DNA adducts, which are not amenable to GC and derivatization owing to the presence of several adjacent polar functional groups. Using LC/ESI-MS/MS and isotope dilution, multiple structurally diverse BD-DNA adducts can be analyzed simultaneously in the same sample with minimal sample preparation.

Authors+Show Affiliations

Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill 27599-7400, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9597770

Citation

Tretyakova NYu, , et al. "Quantitative Analysis of 1,3-butadiene-induced DNA Adducts in Vivo and in Vitro Using Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometry." Journal of Mass Spectrometry : JMS, vol. 33, no. 4, 1998, pp. 363-76.
Tretyakova NYu , Chiang SY, Walker VE, et al. Quantitative analysis of 1,3-butadiene-induced DNA adducts in vivo and in vitro using liquid chromatography electrospray ionization tandem mass spectrometry. J Mass Spectrom. 1998;33(4):363-76.
Tretyakova NYu, ., Chiang, S. Y., Walker, V. E., & Swenberg, J. A. (1998). Quantitative analysis of 1,3-butadiene-induced DNA adducts in vivo and in vitro using liquid chromatography electrospray ionization tandem mass spectrometry. Journal of Mass Spectrometry : JMS, 33(4), 363-76.
Tretyakova NYu , et al. Quantitative Analysis of 1,3-butadiene-induced DNA Adducts in Vivo and in Vitro Using Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometry. J Mass Spectrom. 1998;33(4):363-76. PubMed PMID: 9597770.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Quantitative analysis of 1,3-butadiene-induced DNA adducts in vivo and in vitro using liquid chromatography electrospray ionization tandem mass spectrometry. AU - Tretyakova NYu,, AU - Chiang,S Y, AU - Walker,V E, AU - Swenberg,J A, PY - 1998/5/23/pubmed PY - 2000/6/22/medline PY - 1998/5/23/entrez SP - 363 EP - 76 JF - Journal of mass spectrometry : JMS JO - J Mass Spectrom VL - 33 IS - 4 N2 - 1,3-Butadiene (BD) is a high volume industrial chemical which is known as a multi-site rodent carcinogen and is classified as a probable human carcinogen. Covalent interactions of the reactive epoxy metabolites of BD with DNA lead to the formation of DNA adducts which may cause mutations and tumor formation. In the present work, liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) was employed for analyses of BD-induced DNA adducts in vitro and in vivo. Selected reaction monitoring (SRM) using the fragmentation of the [M + H]+ ions of the adducts to the corresponding protonated nucleobases under collision-induced dissociation was performed. Quantitation was based on isotope dilution with 13C- and 15N-labeled internal standards. The methods were applied in vitro [calf thymus DNA and TK6 cell cultures treated with epoxy metabolites of BD, 3,4-epoxy-1-butene (EB) and diepoxybutane (DEB)] and in vivo [DNA isolated from tissues of BD-exposed laboratory animals]. Two regioisomers of N-7-EB-guanine adducts, N-7-(2-hydroxy-3-buten-1-yl)guanine (N-7-EB-Gua I) and N-7-(1-hydroxy-3-buten-2-yl)guanine (N-7-EB-Gua II) and two N-3-EB-adenine isomers, N-3-(2-hydroxy-3-buten-1-yl)adenine and N-3-(1-hydroxy-3-buten-2-yl)adenine (N-3-EB-Ade I and II), were found in EB-exposed samples. N-7-(2',3',4'-trihydroxybut-1'-yl)guanine (N-7-THB-Gua), N6-(2',3',4'-trihydroxybut-1'-yl)adenine (N6-THB-Ade), and N-3-(2',3',4'-trihydroxybut-1'-yl)adenine (N-3-THB-Ade) were detected in DEB-treated DNA. DNA isolated from liver and lung of rats and mice exposed to 1250 ppm BD for 2 weeks contained both regioisomers of N-7-EB-Gua and N-3-EB-Ade, as well as N-7-THB-Gua and N6-THB-Ade. The methods developed in this work provide the means to study accumulation, repair and dose-response relationships of BD-DNA adducts in vivo. Although less sensitive than gas chromatography/electron capture negative ionization high-resolution mass spectrometry (GC/ECNI-HRMS), LC/ESI(+)-MS/MS in the SRM mode is extremely useful for analysis of BD-DNA adducts, which are not amenable to GC and derivatization owing to the presence of several adjacent polar functional groups. Using LC/ESI-MS/MS and isotope dilution, multiple structurally diverse BD-DNA adducts can be analyzed simultaneously in the same sample with minimal sample preparation. SN - 1076-5174 UR - https://www.unboundmedicine.com/medline/citation/9597770/Quantitative_analysis_of_13_butadiene_induced_DNA_adducts_in_vivo_and_in_vitro_using_liquid_chromatography_electrospray_ionization_tandem_mass_spectrometry_ DB - PRIME DP - Unbound Medicine ER -