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加速器质谱在药理和毒理学研究中的应用。

Applications of accelerator mass spectrometry for pharmacological and toxicological research.

作者信息

Brown Karen, Tompkins Elaine M, White Ian N H

机构信息

Cancer Biomarkers and Prevention Group, Department of Cancer Studies and Molecular Medicine, The Biocentre, University of Leicester, Leicester LE1 7RH, United Kingdom.

出版信息

Mass Spectrom Rev. 2006 Jan-Feb;25(1):127-45. doi: 10.1002/mas.20059.

DOI:10.1002/mas.20059
PMID:16059873
Abstract

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.

摘要

加速器质谱法(AMS)技术以对考古标本进行放射性碳定年而闻名,它通过直接测定样品中的同位素含量而非测量其衰变,彻底改变了药理学和毒理学中的高灵敏度同位素检测。它可以对许多同位素进行定量,包括26Al、14C、41Ca和3H,检测下限可达阿托摩尔(10^(-18))量。通过超低水平的放射性标记已获得人体药代动力学数据。AMS与14C标记的潜在致癌物最令人兴奋的生物医学应用之一是检测组织中修饰的蛋白质或DNA。在啮齿动物和人类中比较了低水平暴露与遗传毒性化学物质共价结合之间的关系。此类化合物包括杂环胺、苯和他莫昔芬。其他应用范围从测量26Al的吸收到监测骨骼中41Ca的周转。在环氧树脂包埋的组织切片中,可以对细胞中的14C标记进行高分辨率成像。随着专门用于生物医学样品分析的仪器的出现,AMS的用途正变得越来越广泛。

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