Quantitation of benzo[a]pyrene-DNA adducts by postlabeling with 14C-acetic anhydride and accelerator mass spectrometry

Radoslav Goldman, Billy W. Day, Tonya A. Carver, Robert J. Mauthe, Ken W Turteltaub, Peter G. Shields

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Quantitation of carcinogen-DNA adducts provides an estimate of the biologically effective dose of a chemical carcinogen reaching the target tissue. In order to improve exposure-assessment and cancer risk estimates, we are developing an ultrasensitive procedure for the detection of carcinogen-DNA adducts. The method is based upon postlabeling of carcinogen-DNA adducts by acetylation with 14C-acetic anhydride combined with quantitation of 14C by accelerator mass spectrometry (AMS). For this purpose, adducts of benzo[a]pyrene-r-7,t-8-dihydrodiol-t-9,10-epoxide (BPDE) with DNA and deoxyguanosine (dG) were synthesized. The most promutagenic adduct of BPDE, 7R,8S,9R-trihydroxy-10S-(N2-deoxyguanosyl)-7,8,9,10-tetrahydrobenzo[a]pyrene (BPdG), was HPLC purified and structurally characterized. Postlabeling of the BPdG adduct with acetic anhydride yielded a major product with a greater than 60% yield. The postlabeled adduct was identified by liquid chromatography-mass spectrometry as pentakis(acetyl) BPdG (AcBPdG). Postlabeling of the BPdG adduct with 14C-acetic anhydride yielded a major product coeluting with an AcBPdG standard. Quantitation of the 14C-postlabeled adduct by AMS promises to allow detection of attomolar amounts of adducts. The method is now being optimized and validated for use in human samples. Copyright (C) 2000 Elsevier Science Ireland Ltd.

Original languageEnglish (US)
Pages (from-to)171-183
Number of pages13
JournalChemico-Biological Interactions
Volume126
Issue number3
DOIs
StatePublished - Jun 1 2000
Externally publishedYes

Fingerprint

Carcinogens
Particle accelerators
Mass spectrometry
DNA Adducts
Mass Spectrometry
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide
Acetylation
Deoxyguanosine
Benzo(a)pyrene
Epoxy Compounds
Liquid chromatography
Liquid Chromatography
High Pressure Liquid Chromatography
Tissue
benzo(a)pyrene-DNA adduct
acetic anhydride
DNA
Neoplasms

Keywords

  • C-postlabeling
  • Benzo[a]pyrene
  • Carcinogenesis
  • DNA adduct
  • Molecular epidemiology

ASJC Scopus subject areas

  • Toxicology

Cite this

Quantitation of benzo[a]pyrene-DNA adducts by postlabeling with 14C-acetic anhydride and accelerator mass spectrometry. / Goldman, Radoslav; Day, Billy W.; Carver, Tonya A.; Mauthe, Robert J.; Turteltaub, Ken W; Shields, Peter G.

In: Chemico-Biological Interactions, Vol. 126, No. 3, 01.06.2000, p. 171-183.

Research output: Contribution to journalArticle

Goldman, Radoslav ; Day, Billy W. ; Carver, Tonya A. ; Mauthe, Robert J. ; Turteltaub, Ken W ; Shields, Peter G. / Quantitation of benzo[a]pyrene-DNA adducts by postlabeling with 14C-acetic anhydride and accelerator mass spectrometry. In: Chemico-Biological Interactions. 2000 ; Vol. 126, No. 3. pp. 171-183.
@article{0d891a0314894880800937c655505adb,
title = "Quantitation of benzo[a]pyrene-DNA adducts by postlabeling with 14C-acetic anhydride and accelerator mass spectrometry",
abstract = "Quantitation of carcinogen-DNA adducts provides an estimate of the biologically effective dose of a chemical carcinogen reaching the target tissue. In order to improve exposure-assessment and cancer risk estimates, we are developing an ultrasensitive procedure for the detection of carcinogen-DNA adducts. The method is based upon postlabeling of carcinogen-DNA adducts by acetylation with 14C-acetic anhydride combined with quantitation of 14C by accelerator mass spectrometry (AMS). For this purpose, adducts of benzo[a]pyrene-r-7,t-8-dihydrodiol-t-9,10-epoxide (BPDE) with DNA and deoxyguanosine (dG) were synthesized. The most promutagenic adduct of BPDE, 7R,8S,9R-trihydroxy-10S-(N2-deoxyguanosyl)-7,8,9,10-tetrahydrobenzo[a]pyrene (BPdG), was HPLC purified and structurally characterized. Postlabeling of the BPdG adduct with acetic anhydride yielded a major product with a greater than 60{\%} yield. The postlabeled adduct was identified by liquid chromatography-mass spectrometry as pentakis(acetyl) BPdG (AcBPdG). Postlabeling of the BPdG adduct with 14C-acetic anhydride yielded a major product coeluting with an AcBPdG standard. Quantitation of the 14C-postlabeled adduct by AMS promises to allow detection of attomolar amounts of adducts. The method is now being optimized and validated for use in human samples. Copyright (C) 2000 Elsevier Science Ireland Ltd.",
keywords = "C-postlabeling, Benzo[a]pyrene, Carcinogenesis, DNA adduct, Molecular epidemiology",
author = "Radoslav Goldman and Day, {Billy W.} and Carver, {Tonya A.} and Mauthe, {Robert J.} and Turteltaub, {Ken W} and Shields, {Peter G.}",
year = "2000",
month = "6",
day = "1",
doi = "10.1016/S0009-2797(00)00160-5",
language = "English (US)",
volume = "126",
pages = "171--183",
journal = "Chemico-Biological Interactions",
issn = "0009-2797",
publisher = "Elsevier Ireland Ltd",
number = "3",

}

TY - JOUR

T1 - Quantitation of benzo[a]pyrene-DNA adducts by postlabeling with 14C-acetic anhydride and accelerator mass spectrometry

AU - Goldman, Radoslav

AU - Day, Billy W.

AU - Carver, Tonya A.

AU - Mauthe, Robert J.

AU - Turteltaub, Ken W

AU - Shields, Peter G.

PY - 2000/6/1

Y1 - 2000/6/1

N2 - Quantitation of carcinogen-DNA adducts provides an estimate of the biologically effective dose of a chemical carcinogen reaching the target tissue. In order to improve exposure-assessment and cancer risk estimates, we are developing an ultrasensitive procedure for the detection of carcinogen-DNA adducts. The method is based upon postlabeling of carcinogen-DNA adducts by acetylation with 14C-acetic anhydride combined with quantitation of 14C by accelerator mass spectrometry (AMS). For this purpose, adducts of benzo[a]pyrene-r-7,t-8-dihydrodiol-t-9,10-epoxide (BPDE) with DNA and deoxyguanosine (dG) were synthesized. The most promutagenic adduct of BPDE, 7R,8S,9R-trihydroxy-10S-(N2-deoxyguanosyl)-7,8,9,10-tetrahydrobenzo[a]pyrene (BPdG), was HPLC purified and structurally characterized. Postlabeling of the BPdG adduct with acetic anhydride yielded a major product with a greater than 60% yield. The postlabeled adduct was identified by liquid chromatography-mass spectrometry as pentakis(acetyl) BPdG (AcBPdG). Postlabeling of the BPdG adduct with 14C-acetic anhydride yielded a major product coeluting with an AcBPdG standard. Quantitation of the 14C-postlabeled adduct by AMS promises to allow detection of attomolar amounts of adducts. The method is now being optimized and validated for use in human samples. Copyright (C) 2000 Elsevier Science Ireland Ltd.

AB - Quantitation of carcinogen-DNA adducts provides an estimate of the biologically effective dose of a chemical carcinogen reaching the target tissue. In order to improve exposure-assessment and cancer risk estimates, we are developing an ultrasensitive procedure for the detection of carcinogen-DNA adducts. The method is based upon postlabeling of carcinogen-DNA adducts by acetylation with 14C-acetic anhydride combined with quantitation of 14C by accelerator mass spectrometry (AMS). For this purpose, adducts of benzo[a]pyrene-r-7,t-8-dihydrodiol-t-9,10-epoxide (BPDE) with DNA and deoxyguanosine (dG) were synthesized. The most promutagenic adduct of BPDE, 7R,8S,9R-trihydroxy-10S-(N2-deoxyguanosyl)-7,8,9,10-tetrahydrobenzo[a]pyrene (BPdG), was HPLC purified and structurally characterized. Postlabeling of the BPdG adduct with acetic anhydride yielded a major product with a greater than 60% yield. The postlabeled adduct was identified by liquid chromatography-mass spectrometry as pentakis(acetyl) BPdG (AcBPdG). Postlabeling of the BPdG adduct with 14C-acetic anhydride yielded a major product coeluting with an AcBPdG standard. Quantitation of the 14C-postlabeled adduct by AMS promises to allow detection of attomolar amounts of adducts. The method is now being optimized and validated for use in human samples. Copyright (C) 2000 Elsevier Science Ireland Ltd.

KW - C-postlabeling

KW - Benzo[a]pyrene

KW - Carcinogenesis

KW - DNA adduct

KW - Molecular epidemiology

UR - http://www.scopus.com/inward/record.url?scp=0034195193&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034195193&partnerID=8YFLogxK

U2 - 10.1016/S0009-2797(00)00160-5

DO - 10.1016/S0009-2797(00)00160-5

M3 - Article

VL - 126

SP - 171

EP - 183

JO - Chemico-Biological Interactions

JF - Chemico-Biological Interactions

SN - 0009-2797

IS - 3

ER -