Accelerator mass spectrometry in the biomedical sciences: applications in low-exposure biomedical and environmental dosimetry

We are utilizing accelerator mass spectrometry as a sensitive detector for tracking the disposition of radioisotopically labeled molecules in the biomedical sciences. These applications have shown the effectiveness of AMS as a tool to quantify biologically important molecules at extremely low levels. For example, AMS is being used to determine the amount of carcinogen covalently bound to animal DNA (DNA adduct) at levels relevent to human exposure. Detection sensitivities are 1 carcinogen molecule bound in 1011 to 1012 DNA bases, depending on the specific activity of the radiolabeled carcinogen. Studies have been undertaken in our laboratory utilizing heterocyclic amine food-borne carcinogens and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent environmental carcinogen, to study the metabolism of carcinogens at low doses. In addition, AMS is being used to detect the presence of rare proteins (mutant forms of protamine) in human sperm. Approximately l per 106 sperm analyzed contain the rare form of the protamine. Protamine isolated from this small number of cells is being analyzed by AMS, following 14C labeling. Thus, AMS can be used to verify the identity of an extremely small amount of biological material. Furthermore, an additional improvement of 2 orders of magnitude in the sensitivity of biomédical tracer studies is suggested by preliminary work with bacterial hosts depleted in radiocarbon. Other problems in the life sciences where detection sensitivity or sample sizes are limitations should also benefit from AMS. Studies are underway to measure the molecular targeting of cancer chemotherapeutics in human tissue and to pursue applications for receptor biology. We are also applying other candidate isotopes, such as ³H (double labeling with ¹⁴C) and ⁴¹Ca (bone absorption) to problems in biology. The detection of ³⁶Cl and ²⁶Al have applications for determination of human neutron exposure and understanding neurological toxicity, respectively. The results described here with ¹⁴C-labeled molecules coupled with new isotope applications clearly show AMS technology to be an important new tool for the biomedical sciences community.