Oral administration of PCBs induces proinflammatory and prometastatic responses

Abstract

Exposure to specific congeners of polychlorinated biphenyls (PCBs) can induce proinflammatory alterations, which may contribute to the formation of blood-borne tumor metastasis. The main aim of the present study was to establish an experimental model of PCB exposure in which PCBs are administered by oral gavage, which resembles the human exposure through the food chain. To determine structure-function relationship, we studied induction of inflammatory responses in the livers, lungs and brains of mice treated with PCB77 (a major coplanar PCB), PCB104 (a non-coplanar PCB with multiple ortho-chlorine substituents), and PCB153 (a major non-coplanar PCB) after a single gavage dose (150 µmol/kg body weight). The strongest expression of proinflammatory proteins occurred 24 h following the PCB administration independent of the class of PCB congeners. These data indicate that food-chain exposure to PCBs can induce proinflammatory mediators in organs that are potential targets for PCB-induced toxicity.

Blood dendritic cells in cattle infected with bovine leukemia virus (BLV): isolation and phenotyping

“…Among ortho-substituted PCBs, 2,2',4,5,6'-pentachlorobiphenyl (PCB104) also affects tight junction proteins expression in brain endothelial cells, stimulates inflammatory mediators in vascular endothelial cells and induces prometastatic responses (Choi et al 2003, Sipka et al 2008. It has been demonstrated that vascular endothelial growth factor (VEGF) is involved in PCB104 induced endothelial hyperpermeability (Eum et al 2004).…”

“…Studies on PCB toxicity are mainly based on in vitro models or in vitro experiments in which mice or rats are intraperitoneally injected with PCBs (Sipka et al 2008). The in vivo effects of PCB153 and PCB104 on expression of the VEGF system in the CP in domestic animals exposed to PCBs through the food chain, the most common route of PCB exposure, has not yet been reported.…”

“…There is evidence that PCB153 disrupts expression of tight junction proteins in the blood-brain barrier which restricts most paracellular movement of ions and solutes across the brain barriers (Eum et al 2008, Seelbach et al 2010. Among ortho-substituted PCBs, 2,2',4,5,6'-pentachlorobiphenyl (PCB104) also affects tight junction proteins expression in brain endothelial cells, stimulates inflammatory mediators in vascular endothelial cells and induces prometastatic responses (Choi et al 2003, Sipka et al 2008.…”

Polychlorinated Biphenyls and Polybrominated Biphenyls

“…PCB-77, PCB-104 and PCB-153 induced expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and monocyte chemoattractant protein-1 (MCP-1) in the liver, lung, and brain of male C57Bl/6 mice. PCB-77 and PCB-104 also increased levels of matrix metalloproteinase-7 (MMP-7) mRNA in the liver and brain (Sipka et al, 2008).…”

“…In addition to the core groups, inflammation, albeit of low incidence and intensity, was also observed in the control groups in the studies with PCB-118 and PCB-126, and in the uterus of rats in the PCB-153 control group, but not in the ovary of rats in the same group. Sipka et al (2008) investigated the potential for various PCB congeners to induce inflammation in mice. Mice were given a single gavage dose (150 μmol/kg bw) of PCB-77, PCB-104, or PCB-153.…”