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

Journal Article · Sun Jul 01 04:00:00 EDT 1990 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.87.14.5288· OSTI ID:6151460

Turteltaub, K W; Felton, J S; Gledhill, B L; Vogel, J S; Southon, J R; Caffee, M W; Finkel, R C; Proctor, I D; Davis, J C ^[1]; Nelson, D E ^[2]

---

1. Lawrence Livermore National Laboratory, CA (USA)
2. Lawrence Livermore National Laboratory, CA (USA) Simon Fraser Univ., Brunaby, British Columbia (Canada)

Accelerator mass 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 {sup 14}C-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 ({sup 10}Be, {sup 14}C, {sup 26}Al, {sup 41}Ca, and {sup 129}I) 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-{sup 14}C)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. Formation of adducts is linearly dependent on dose down to an exposure of 500 ng per kg of body weight. With the present measurements, the authors demonstrate at least 1 order of magnitude improvement over the best adduct detection sensitivity reported to data and 3-5 orders of magnitude improvement over other methods used for adduct measurement. Expanded applications involving human subjects, including clinical applications, are now expected because of the great detection sensitivity and small sample size requirements of AMS.

• OSTI ID: 6151460
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 87:14; ISSN PNASA; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADDUCTS
AMINES
ANIMALS
BACTERIA
BODY
CARBON 14 COMPOUNDS
CARCINOGENS
CHRONIC EXPOSURE
DIGESTIVE SYSTEM
DNA ADDUCTS
DOSE-RESPONSE RELATIONSHIPS
GLANDS
LABELLED COMPOUNDS
LIVER
MAMMALS
MAN
MASS SPECTROMETERS
MASS SPECTROSCOPY
MEASURING INSTRUMENTS
MICE
MICROORGANISMS
ORGANIC COMPOUNDS
ORGANS
POLYCYCLIC AROMATIC AMINES
PRIMATES
RODENTS
SENSITIVITY
SPECTROMETERS
SPECTROSCOPY
VERTEBRATES