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DEHP, bis(2)-ethylhexyl phthalate, alters gene expression in human cells: possible correlation with initiation of fetal developmental abnormalities | Academic Article individual record
abstract

Diethylhexylphthalate (DEHP) is a widely distributed phthalate, to which humans are exposed to due to its variety of commercial and manufacturing uses. As a plasticiser, it is found in a wide number of products, and metabolites of DEHP have been detected in urine samples from a high percentage of the people screened for phthalates. We utilised DNA microarray analysis to evaluate DEHP for gene expression disrupting activity using the human cell line MCF-7, and found that DEHP significantly dysregulated approximately 34% of the 2400 genes spotted on the NEN2400 chip we used. The results suggest that DEHP, a known estrogen agonist and probable androgen antagonist, alters the expression of a number of genes, many of which are critical for fetal development. Down-regulation of two genes, FGD1 and PAFAH1B1, related in that both are essential for fetal brain development, was corroborated using quantitative real time PCR. These studies show DEHP to be a highly effective human gene expression-altering chemical, and that, at appropriate concentrations, it has the possibility of altering fetal central nervous system development, resulting in the birth defects lissencephaly and/or faciodigitogenital dysplasia.

author list (cited authors)
Hokanson, R., Hanneman, W., Hennessey, M., Donnelly, K. C., McDonald, T., Chowdhary, R., & Busbee, D. L.
publication date
2006
publisher
published in
keywords
  • Fetal Development
  • Abnormalities, Multiple
  • Guanine Nucleotide Exchange Factors
  • Cell Line, Tumor
  • Health Effects Induced By Environmental Chemicals
  • Dose-Response Relationship, Drug
  • Plasticiser, Real Time PCR
  • Gas Chromatography-Mass Spectrometry
  • Water Pollutants, Chemical
  • Abnormalities, Drug-Induced
  • Molecular Structure
  • Real Time PCR
  • Plasticizers
  • Oligonucleotide Array Sequence Analysis
  • Gene Expression Profiling
  • Plasticiser
  • DNA Microarray Analysis
  • Endocrine Disruptors
  • Gene Expression Regulation
  • Central Nervous System
  • Humans
  • 1-Alkyl-2-acetylglycerophosphocholine Esterase
  • Diethylhexyl Phthalate
  • Fresh Water
  • Texas
  • Down-Regulation
  • Gene Expression
  • Polymerase Chain Reaction
  • Microtubule-Associated Proteins
citation count

30