Applications of accelerator mass spectrometry for pharmacological and toxicological research.
The technique of accelerator mass spectrometry (AMS), known for radiocarbon dating of archeological specimens, has revolutionized high-sensitivity isotope detection in pharmacology and toxicology by allowing the direct determination of the amount of isotope in a sample rather than measuring its decay. It can quantify many isotopes, including 26Al, 14C, 41Ca, and 3H with detection down to attomole (10(-18)) amounts. Pharmacokinetic data in humans have been achieved with ultra-low levels of radiolabel. One of the most exciting biomedical applications of AMS with 14C-labeled potential carcinogens is the detection of modified proteins or DNA in tissues. The relationship between low-level exposure and covalent binding of genotoxic chemicals has been compared in rodents and humans. Such compounds include heterocyclic amines, benzene, and tamoxifen. Other applications range from measuring the absorption of 26Al to monitoring 41Ca turnover in bone. In epoxy-embedded tissue sections, high-resolution imaging of 14C label in cells is possible. The uses of AMS are becoming more widespread with the availability of instrumentation dedicated to the analysis of biomedical samples.
Brown
Karen
K
Cancer Biomarkers and Prevention Group, Department of Cancer Studies and Molecular Medicine, The Biocentre, University of Leicester, Leicester LE1 7RH, United Kingdom.
Tompkins
Elaine M
EM
White
Ian N H
IN
D000818:Animals; D035843:Biomedical Research; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000378:metabolism*; D006801:Humans; D007554:Isotopes / Q000032:analysis; D013058:Mass Spectrometry / Q000379:methods*; D004364:Pharmaceutical Preparations; D010599:Pharmacokinetics; D018675:Toxicity Tests / Q000379:methods*
D007554:Isotopes; D004364:Pharmaceutical Preparations