Polychlorinated biphenyl 153 alters the intestinal epithelial cell transcriptome

Area of Science:

• Environmental Health
• Toxicology
• Molecular Biology

Background:

• Polychlorinated biphenyl 153 (PCB153) is a persistent environmental pollutant found in human tissues.
• Dietary exposure is a primary route for PCB153 accumulation.
• The intestinal epithelium is a key target for PCB toxicity, but mechanisms are unclear.

Purpose of the Study:

• To investigate the molecular effects of PCB153 on human intestinal epithelial cells (IECs).
• To identify key biological pathways disrupted by PCB153 exposure.
• To establish a transcriptomic framework for understanding PCB toxicity in the gut.

Main Methods:

• Transcriptomic profiling of non-transformed human intestinal epithelial cells (IECs).
• Dose-dependent exposure to PCB153.
• Analysis of gene expression alterations and affected signaling pathways.

Main Results:

• PCB153 induced dose-dependent changes in the IEC transcriptome.
• Affected pathways include Wnt signaling, ABC transporters, cGMP-PKG signaling, and metal homeostasis.
• High-dose PCB153 activated inflammatory (TNF, NF-κB) and tumorigenic pathways.
• Mitochondrial metabolism, oxidative phosphorylation, and detoxification were suppressed.

Conclusions:

• PCB153 causes extensive transcriptomic remodeling in normal human IECs.
• PCB153 disrupts intestinal regeneration, immune response, and metabolic regulation.
• Findings provide mechanistic insights into PCB153-induced intestinal damage and potential biomarkers/targets.