Radioanalytical and nuclear techniques in trace metal toxicology research

Trace metal toxicology research aimed at generating human-relevant information for risk assessment requires the use of sensitive and sophisticated analytical techniques to determine typically µg kg−1 or lower concentrations of trace metals in tissues, cells, intracellular components of laboratory animals and humans. The results of these techniques are needed for an understanding of the biochemical mechanisms and bio-transformations involving trace metals. In this context, radioanalytical and nuclear methods plays a pivotal role. In order to give an idea of typical results which can be obtained by radioanalytical and nuclear techniques when used in combination with biochemical and molecular biology techniques of cellular fractionation we report here some typical studies carried out by means of non-carrier added radiotracers with high specific activity, and neutron activation analysis (NAA). The investigations have been performed in the context of an integrated and complementary in vivo and in vitro approach that uses both animal and human test systems. Applications reported concern: (1) the in vivo work on laboratory animals (brain regional thallium distribution in rats and identification of thallium binders in testis, by means of 201+202Tl); (2) in vitro investigations on cells of animal origin (arsenic uptake and biomethylation in rat brain aggregates, neurons, microglia and astrocytes as well as speciation of vanadate in Balb/3T3 cells, by means of 73As and 48V, respectively); (3) in vitro experiments on cell of human origin (intracellular behavior of cadmium in human umbilical cord blood stem cells, by means of 109Cd); (4) analytical determinations of trace metals in tissues of general population and patients potentially affected by metal-related disease, by means of NAA. The analytical determinations carried out allowed to relate total element concentrations in cells to the results of investigations at the intracellular and molecular levels with the goal of identifying the biochemical components that interact with trace metals. These findings demonstrate the great potential of radioanalytical and nuclear techniques in the context of an integrated in vivo-in vitro strategy adopted in trace metal toxicology research for a mechanistically-based hazard characterization concerning the exposure to low doses of trace metals