Intestinal exposure to PCB 153 induces inflammation via the ATM/NEMO pathway

Area of Science:

• Toxicology
• Gastroenterology
• Environmental Health

Background:

• Polychlorinated biphenyls (PCBs) are persistent organic pollutants with known adverse health effects.
• PCBs bio-accumulate in food sources, leading to dietary exposure in humans.
• The gut's role in PCB toxicity, particularly concerning inflammation and barrier function, remains understudied.

Purpose of the Study:

• To investigate the impact of PCB 153 on intestinal permeability and inflammation.
• To elucidate the underlying mechanisms of PCB 153-induced intestinal damage.
• To assess the genotoxicity of PCB 153 on intestinal epithelial cells.

Main Methods:

• Mice were orally exposed to PCB 153 to assess intestinal permeability and inflammation.
• Intestinal epithelial cells (IECs) were analyzed for genotoxicity and inflammatory markers.
• Human IEC line (SW480) was used to study direct effects of PCB 153, measuring NF-κB activation, DNA damage, and cytokine expression.

Main Results:

• Oral PCB 153 exposure increased intestinal permeability and inflammatory cytokine expression in mice.
• Genotoxic damage and NF-κB activation were observed in the inflamed intestinal epithelium.
• PCB 153 exposure in human IECs mirrored in vivo findings, with ATM/NEMO pathway activation upstream of NF-κB.

Conclusions:

• Oral PCB 153 exposure is genotoxic to intestinal epithelial cells.
• PCB 153 induces intestinal inflammation and barrier dysfunction.
• The ATM/NEMO pathway activation is a key mechanism in PCB 153-induced intestinal toxicity.