DEHP, bis(2)-ethylhexyl phthalate, alters gene expression in human cells: possible correlation with initiation of fetal developmental abnormalities.
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.
Hokanson
R
R
Department of Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843, USA.
Hanneman
W
W
Hennessey
M
M
Donnelly
K C
KC
McDonald
T
T
Chowdhary
R
R
Busbee
D L
DL
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000378:metabolism; D000014:Abnormalities, Drug-Induced / Q000235:genetics / Q000378:metabolism*; D000015:Abnormalities, Multiple / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002490:Central Nervous System / Q000002:abnormalities; D004051:Diethylhexyl Phthalate / Q000032:analysis / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D052244:Endocrine Disruptors / Q000633:toxicity; D047109:Fetal Development / Q000187:drug effects*; D005618:Fresh Water / Q000737:chemistry; D008401:Gas Chromatography-Mass Spectrometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D015394:Molecular Structure; D020411:Oligonucleotide Array Sequence Analysis; D010968:Plasticizers / Q000032:analysis / Q000633:toxicity*; D016133:Polymerase Chain Reaction / Q000379:methods; D013781:Texas; D014874:Water Pollutants, Chemical / Q000032:analysis / Q000633:toxicity*
D052244:Endocrine Disruptors; C490796:FGD1 protein, human; D020662:Guanine Nucleotide Exchange Factors; D008869:Microtubule-Associated Proteins; D010968:Plasticizers; D014874:Water Pollutants, Chemical; D004051:Diethylhexyl Phthalate; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human