DEHP, bis(2)-ethylhexyl phthalate, alters gene expression in human cells: possible correlation with initiation of fetal developmental abnormalities.

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.

• Authors: R Hokanson, W Hanneman, M Hennessey, K C Donnelly, T McDonald, R Chowdhary, D L Busbee
• Journal: Human & experimental toxicology (Hum Exp Toxicol) Vol. 25 Issue 12 Pg. 687-95 (Dec 2006) ISSN: 0960-3271 [Print] England
• PMID: 17286146 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Endocrine Disruptors
• FGD1 protein, human
• Guanine Nucleotide Exchange Factors
• Microtubule-Associated Proteins
• Plasticizers
• Water Pollutants, Chemical
• Diethylhexyl Phthalate
• 1-Alkyl-2-acetylglycerophosphocholine Esterase
• PAFAH1B1 protein, human

Topics

• 1-Alkyl-2-acetylglycerophosphocholine Esterase (metabolism)
• Abnormalities, Drug-Induced (genetics, metabolism)
• Abnormalities, Multiple (genetics, metabolism)
• Cell Line, Tumor
• Central Nervous System (abnormalities)
• Diethylhexyl Phthalate (analysis, toxicity)
• Dose-Response Relationship, Drug
• Down-Regulation (drug effects)
• Endocrine Disruptors (toxicity)
• Fetal Development (drug effects)
• Fresh Water (chemistry)
• Gas Chromatography-Mass Spectrometry
• Gene Expression Profiling
• Gene Expression Regulation (drug effects)
• Guanine Nucleotide Exchange Factors (metabolism)
• Humans
• Microtubule-Associated Proteins (metabolism)
• Molecular Structure
• Oligonucleotide Array Sequence Analysis
• Plasticizers (analysis, toxicity)
• Polymerase Chain Reaction (methods)
• Texas
• Water Pollutants, Chemical (analysis, toxicity)