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

Department of Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843, USA

W Hanneman

M Hennessey

Department of Environmental Health, College of Veterinary Medicine, Colorado State University, Fort Collins, CO 80523, USA

K C Donnelly

Department of Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843, USA; Center for Environmental and Rural Health, Texas A&M University, College Station, TX 77843, USA; Department of Environmental and Industrial Health, School of Rural Public Health, TAMU Health Science Center, Texas A&M University, College Station, TX 77843, USA

T McDonald

Center for Environmental and Rural Health, Texas A&M University, College Station, TX 77843, USA; Department of Environmental and Industrial Health, School of Rural Public Health, TAMU Health Science Center, Texas A&M University, College Station, TX 77843, USA

R Chowdhary

Department of Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843, USA

D L Busbee

Department of Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843, USA; Center for Environmental and Rural Health, Texas A&M University, College Station, TX 77843, USA; Department of Environmental and Industrial Health, School of Rural Public Health, TAMU Health Science Center, Texas A&M University, College Station, TX 77843, USA DBUSBEE{at}cvm.tamu.edu;dbusbee@tamu.edu

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 ofthe peoplescreened 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.

Key Words: DNA microarray analysis • gene expression • health effects induced by environmental chemicals • plasticiser • real time PCR

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