Accelerator mass spectrometry in biomedical dosimetry: Relationship between low-level exposure and covalent binding of heterocyclic amine carcinogens to DNA

Ken W Turteltaub, J. S. Felton, B. L. Gledhill, J. S. Vogel, J. R. Southon, M. W. Caffee, R. C. Finkel, D. E. Nelson, I. D. Proctor, J. C. Davis

Research output: Contribution to journalArticle

174 Citations (Scopus)

Abstract

Accelerator masss spectrometry (AMS) is used to determine the amount of carcinogen covalently bound to mouse liver DNA (DNA adduct) following very low-level exposure to a 14C-labeled carcinogen. AMS is a highly sensitive method for counting long-lived but rare cosmogenic isotopes. While AMS is a tool of importance in the earth sciences, it has not been applied in biomedical research. The ability of AMS to assay rare isotope concentrations (10Be, 14C, 26Al, 41Ca, and 129I) in microgram amounts suggests that extension to the biomedical sciences is a natural and potentially powerful application of the technology. In this study, the relationship between exposure to low levels of 2-amino-3,8-dimethyl[2-14C]imidazo[4,5-f]quinoxaline and formation of DNA adducts is examined to establish the dynamic range of the technique and the potential sensitivity for biological measurements, as well as to evaluate the relationship between DNA adducts and low-dose carcinogen exposure. Instrument reproducibility in this study is 2%; sensitivity is 1 adduct per 1011 nucleotides. Formation of adducts is linearly dependent on dose down to an exposure of 500 ng per kg of body weight. With the present measurements, we demonstrate at least 1 order of magnitude improvement over the best adduct detection sensitivity reported to date and 3-5 orders of magnitude improvement over other methods used for adduct measurement. An additional improvement of 2 orders of magnitude in sensitivity is suggested by preliminary experiments to develop bacterial hosts depleted in radiocarbon. Expanded applications involving human subjects, including clinical applications, are now expected because of the great detection sensitivity and small sample size requirements of AMS.

Original languageEnglish (US)
Pages (from-to)5288-5292
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume87
Issue number14
DOIs
StatePublished - 1990
Externally publishedYes

Fingerprint

Carcinogens
Amines
Mass Spectrometry
Spectrum Analysis
DNA Adducts
DNA
Isotopes
Earth Sciences
Quinoxalines
Sample Size
Biomedical Research
Nucleotides
Body Weight
Technology
Liver

Keywords

  • 2-amino-3,8-dimethylimidazol[4,5-f]quinoxaline
  • C Detection

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Accelerator mass spectrometry in biomedical dosimetry : Relationship between low-level exposure and covalent binding of heterocyclic amine carcinogens to DNA. / Turteltaub, Ken W; Felton, J. S.; Gledhill, B. L.; Vogel, J. S.; Southon, J. R.; Caffee, M. W.; Finkel, R. C.; Nelson, D. E.; Proctor, I. D.; Davis, J. C.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 87, No. 14, 1990, p. 5288-5292.

Research output: Contribution to journalArticle

Turteltaub, Ken W ; Felton, J. S. ; Gledhill, B. L. ; Vogel, J. S. ; Southon, J. R. ; Caffee, M. W. ; Finkel, R. C. ; Nelson, D. E. ; Proctor, I. D. ; Davis, J. C. / Accelerator mass spectrometry in biomedical dosimetry : Relationship between low-level exposure and covalent binding of heterocyclic amine carcinogens to DNA. In: Proceedings of the National Academy of Sciences of the United States of America. 1990 ; Vol. 87, No. 14. pp. 5288-5292.
@article{7eaf599fd3c545a492de770d0ff325d7,
title = "Accelerator mass spectrometry in biomedical dosimetry: Relationship between low-level exposure and covalent binding of heterocyclic amine carcinogens to DNA",
abstract = "Accelerator masss spectrometry (AMS) is used to determine the amount of carcinogen covalently bound to mouse liver DNA (DNA adduct) following very low-level exposure to a 14C-labeled carcinogen. AMS is a highly sensitive method for counting long-lived but rare cosmogenic isotopes. While AMS is a tool of importance in the earth sciences, it has not been applied in biomedical research. The ability of AMS to assay rare isotope concentrations (10Be, 14C, 26Al, 41Ca, and 129I) in microgram amounts suggests that extension to the biomedical sciences is a natural and potentially powerful application of the technology. In this study, the relationship between exposure to low levels of 2-amino-3,8-dimethyl[2-14C]imidazo[4,5-f]quinoxaline and formation of DNA adducts is examined to establish the dynamic range of the technique and the potential sensitivity for biological measurements, as well as to evaluate the relationship between DNA adducts and low-dose carcinogen exposure. Instrument reproducibility in this study is 2{\%}; sensitivity is 1 adduct per 1011 nucleotides. Formation of adducts is linearly dependent on dose down to an exposure of 500 ng per kg of body weight. With the present measurements, we demonstrate at least 1 order of magnitude improvement over the best adduct detection sensitivity reported to date and 3-5 orders of magnitude improvement over other methods used for adduct measurement. An additional improvement of 2 orders of magnitude in sensitivity is suggested by preliminary experiments to develop bacterial hosts depleted in radiocarbon. Expanded applications involving human subjects, including clinical applications, are now expected because of the great detection sensitivity and small sample size requirements of AMS.",
keywords = "2-amino-3,8-dimethylimidazol[4,5-f]quinoxaline, C Detection",
author = "Turteltaub, {Ken W} and Felton, {J. S.} and Gledhill, {B. L.} and Vogel, {J. S.} and Southon, {J. R.} and Caffee, {M. W.} and Finkel, {R. C.} and Nelson, {D. E.} and Proctor, {I. D.} and Davis, {J. C.}",
year = "1990",
doi = "10.1073/pnas.87.14.5288",
language = "English (US)",
volume = "87",
pages = "5288--5292",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "14",

}

TY - JOUR

T1 - Accelerator mass spectrometry in biomedical dosimetry

T2 - Relationship between low-level exposure and covalent binding of heterocyclic amine carcinogens to DNA

AU - Turteltaub, Ken W

AU - Felton, J. S.

AU - Gledhill, B. L.

AU - Vogel, J. S.

AU - Southon, J. R.

AU - Caffee, M. W.

AU - Finkel, R. C.

AU - Nelson, D. E.

AU - Proctor, I. D.

AU - Davis, J. C.

PY - 1990

Y1 - 1990

N2 - Accelerator masss spectrometry (AMS) is used to determine the amount of carcinogen covalently bound to mouse liver DNA (DNA adduct) following very low-level exposure to a 14C-labeled carcinogen. AMS is a highly sensitive method for counting long-lived but rare cosmogenic isotopes. While AMS is a tool of importance in the earth sciences, it has not been applied in biomedical research. The ability of AMS to assay rare isotope concentrations (10Be, 14C, 26Al, 41Ca, and 129I) in microgram amounts suggests that extension to the biomedical sciences is a natural and potentially powerful application of the technology. In this study, the relationship between exposure to low levels of 2-amino-3,8-dimethyl[2-14C]imidazo[4,5-f]quinoxaline and formation of DNA adducts is examined to establish the dynamic range of the technique and the potential sensitivity for biological measurements, as well as to evaluate the relationship between DNA adducts and low-dose carcinogen exposure. Instrument reproducibility in this study is 2%; sensitivity is 1 adduct per 1011 nucleotides. Formation of adducts is linearly dependent on dose down to an exposure of 500 ng per kg of body weight. With the present measurements, we demonstrate at least 1 order of magnitude improvement over the best adduct detection sensitivity reported to date and 3-5 orders of magnitude improvement over other methods used for adduct measurement. An additional improvement of 2 orders of magnitude in sensitivity is suggested by preliminary experiments to develop bacterial hosts depleted in radiocarbon. Expanded applications involving human subjects, including clinical applications, are now expected because of the great detection sensitivity and small sample size requirements of AMS.

AB - Accelerator masss spectrometry (AMS) is used to determine the amount of carcinogen covalently bound to mouse liver DNA (DNA adduct) following very low-level exposure to a 14C-labeled carcinogen. AMS is a highly sensitive method for counting long-lived but rare cosmogenic isotopes. While AMS is a tool of importance in the earth sciences, it has not been applied in biomedical research. The ability of AMS to assay rare isotope concentrations (10Be, 14C, 26Al, 41Ca, and 129I) in microgram amounts suggests that extension to the biomedical sciences is a natural and potentially powerful application of the technology. In this study, the relationship between exposure to low levels of 2-amino-3,8-dimethyl[2-14C]imidazo[4,5-f]quinoxaline and formation of DNA adducts is examined to establish the dynamic range of the technique and the potential sensitivity for biological measurements, as well as to evaluate the relationship between DNA adducts and low-dose carcinogen exposure. Instrument reproducibility in this study is 2%; sensitivity is 1 adduct per 1011 nucleotides. Formation of adducts is linearly dependent on dose down to an exposure of 500 ng per kg of body weight. With the present measurements, we demonstrate at least 1 order of magnitude improvement over the best adduct detection sensitivity reported to date and 3-5 orders of magnitude improvement over other methods used for adduct measurement. An additional improvement of 2 orders of magnitude in sensitivity is suggested by preliminary experiments to develop bacterial hosts depleted in radiocarbon. Expanded applications involving human subjects, including clinical applications, are now expected because of the great detection sensitivity and small sample size requirements of AMS.

KW - 2-amino-3,8-dimethylimidazol[4,5-f]quinoxaline

KW - C Detection

UR - http://www.scopus.com/inward/record.url?scp=0025062962&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025062962&partnerID=8YFLogxK

U2 - 10.1073/pnas.87.14.5288

DO - 10.1073/pnas.87.14.5288

M3 - Article

C2 - 2371271

AN - SCOPUS:0025062962

VL - 87

SP - 5288

EP - 5292

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 14

ER -