Applications of accelerator mass spectrometry for pharmacological and toxicological research

被引:42
作者
Brown, K
Tompkins, EM
White, INH [1 ]
机构
[1] Univ Leicester, Dept Canc Studies & Mol Med, MRC, Mol Endocrinol Grp, Leicester LE2 7LX, Leics, England
[2] Univ Leicester, Bioctr, Dept Canc Studies & Mol Med, Canc Biomarkers & Prevent Grp, Leicester LE1 7RH, Leics, England
关键词
accelerator mass spectrometry; radiolabel; microdosing; pharmacokinetics; DNA binding;
D O I
10.1002/mas.20059
中图分类号
O433 [光谱学];
学科分类号
0703 ; 070302 ;
摘要
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 Al-26, C-14, Ca-41, and H-3 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 C-14-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 Al-26 to monitoring Ca-41 turnover in bone. In epoxy-embedded tissue sections, high-resolution imaging of C-14 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. (C) 2005 Wiley Periodicals, Inc.
引用
收藏
页码:127 / 145
页数:19
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