Klaren WD, Vine D, Vogt S, Robertson LW. Evaluation of the spatial distribution of hepatic metals following PCB126 exposure with x-ray fluorescence microscopy. Society of Toxicology Annual Meeting, New Orleans, La, 2016.
Animal studies have shown that exposure to the environmental pollutant and AhR agonist 3,3’,4,4’,5-pentachlorobiphenyl (PCB126) causes alterations in hepatic metals and micronutrients, in particular: copper, zinc, and manganese. Previous investigations into these effects used acid digested liver tissue employing inductively coupled plasma mass spectrometry (ICP-MS) or a similar analytical techniques. Although informative, these techniques lack the spatial distribution of the metals, within the tissue. Studies have shown that the hepatotoxicity of PCB126 is particularly focused in specific areas. This suggests that the greatest degree of metal disruption may be in the region nearest to this localized hepatic injury. X-ray fluorescence microscopy (XFM) is a powerful technique that allows for the spatial distribution of metals to be ascertained on a tissue/cellular level. Male, Sprague-Dawley rats were fed a modified AIN-93G diet for three weeks, to reach micronutrient equilibrium. The rats were then given a single intraperitoneal injection of either tocopherol-stripped soy oil (5mL/kg), 1 μmol/kg PCB126 or 5 μmol/kg PCB126 in soy oil. After two weeks of exposure, the animals were sacrificed and organs collected. Unstained, formalin fixed, paraffin embedded, sections were placed on silicon-nitride grids and dried in a desiccator. XFM was carried out at the Advanced Photon Source at Argonne National Laboratory. Metal gradients between the central vein and portal triad were seen, especially with copper and iron. Interestingly, clusters of high concentrations of zinc were seen which appear to be in the extracellular space. Differences were seen in animals exposed to PCB126. XFM proves to be a dynamic tool for exploring the micronutrient disruption within a tissue and how toxicants, in particular PCB126, can disrupt this distribution.