Klaren WD, Robertson LW. PCB126-mediated disruption of hepatic metal homeostasis in mice and the role of metallothionein. Society of Toxicology Annual Meeting, San Diego, Ca, 2015.
Polychlorinated biphenyls (PCBs), industrial chemicals and persistent environmental pollutants, are found in rural and urban settings. Rodent studies have shown that exposure to PCB126, a dioxin-like PCB, causes a significant disruption of hepatic metals homeostasis and an increase in metallothionein (MT), an antioxidant protein and metal carrier. The current study investigates this phenomenon in a MT knockout mouse strain in order to assess the role of metallothionein in this disruption. Twenty four 129S male mice were obtained from Jackson labs (12 wild type (WT) and 12 MT knockout (KO)) and placed on a purified diet (AIN-93G) for 3 weeks to achieve hepatic metal equilibrium. Mice were then given a single injection, IP, of either soy oil or 150 umol/kg PCB126 in soy oil. The animals were sacrificed 2 weeks later and organs processed for analysis. The expression of MTI, MTII, and classic AhR regulated genes were investigated by qRT-PCR and western blotting and hepatic metals status determined by inductively coupled plasma mass spectroscopy (ICP-MS). Also intracellular metals status was investigated using energy dispersive spectroscopy transmission electron microscopy (EDS-TEM). Liver tissue was also analyzed histologically. Liver weights increased with PCB126 exposure, typically considered a hallmark of PCB126 exposure, however no difference was seen between WT and KO. Metallothionein was seen to increase with PCB126 exposure as expected and was not seen in the KO. Hepatic metals levels (Cu, Zn, Mn and Se) were investigated and their distribution follows a similar pattern of modulation as has been seen before, both within the cell (EDS-TEM) and within the organ (ICP-MS). Histologically, the liver shows signs of steatosis in PCB126 treated animals. Given its role in metal homeostasis, metallothionein has been shown to modulate metal status by its induction; this research suggests that MT may not be the sole cause of the metal disruption caused by PCB126 exposure.