Transcriptional profiling and biological pathway analysis of human equivalence PCB exposure in vitro: indicator of disease and disorder development in humans

Environ Res. 2015 Apr:138:202-16. doi: 10.1016/j.envres.2014.12.031. Epub 2015 Feb 27.

Abstract

Background and aims: Our earlier gene-expression studies with a Slovak PCBs-exposed population have revealed possible disease and disorder development in accordance with epidemiological studies. The present investigation aimed to develop an in vitro model system that can provide an indication of disrupted biological pathways associated with developing future diseases, well in advance of the clinical manifestations that may take years to appear in the actual human exposure scenario.

Methods: We used human Primary Blood Mononuclear Cells (PBMC) and exposed them to a mixture of human equivalence levels of PCBs (PCB-118, -138, -153, -170, -180) as found in the PCBs-exposed Slovak population. The microarray studies of global gene expression were conducted on the Affymetrix platform using Human Genome U133 Plus 2.0 Array along with Ingenuity Pathway Analysis (IPA) to associate the affected genes with their mechanistic pathways. High-throughput qRT-PCR Taqman Low Density Array (TLDA) was done to further validate the selected 6 differentially expressed genes of our interest, viz., ARNT, CYP2D6, LEPR, LRP12, RRAD, TP53, with a small population validation sample (n=71).

Results: Overall, we revealed a discreet gene expression profile in the experimental model that resembled the diseases and disorders observed in PCBs-exposed population studies. The disease pathways included endocrine system disorders, genetic disorders, metabolic diseases, developmental disorders, and cancers, strongly consistent with the evidence from epidemiological studies.

Interpretation: These gene finger prints could lead to the identification of populations and subgroups at high risk for disease, and can pose as early disease biomarkers well ahead of time, before the actual disease becomes visible.

Keywords: Biomarkers; Disease and disorders; Gene expression; Human PBMC; PCBs; Pathway analysis; Taqman Low-Density Array (TLDA).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Biomarkers / blood
  • Child
  • District of Columbia
  • Environmental Exposure*
  • Environmental Pollutants / toxicity*
  • Female
  • Gene Expression Regulation / drug effects*
  • Humans
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Molecular Sequence Data
  • Oligonucleotide Array Sequence Analysis
  • Polychlorinated Biphenyls / toxicity*
  • Real-Time Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Slovakia
  • Transcriptome
  • Young Adult

Substances

  • Biomarkers
  • Environmental Pollutants
  • Polychlorinated Biphenyls

Associated data

  • GEO/GSE22668