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Toxicol Appl Pharmacol

Title:		Gene expression changes induced in mouse liver by di(2-ethylhexyl) phthalate
Author(s):		Wong JS; Gill SS;
Address:		"Department of Cell Biology and Neuroscience, University of California, Riverside 92521, USA"
Journal Title:		Toxicol Appl Pharmacol
Year:		2002
Volume:		185
Issue:		3
Page Number:		180 - 196
DOI:		10.1006/taap.2002.9540
ISSN/ISBN:		0041-008X (Print) 0041-008X (Linking)
Abstract:		"Increasing chemical use necessitates a better understanding of how pollutants, such as di(2-ethylhexyl) phthalate (DEHP), a peroxisome proliferator and a phthalate plasticizer, affect human health. To understand the effects of DEHP exposure, we utilized microarray technology to identify novel DEHP targets in livers of male C57BL/6 mice treated with 1.0% dietary DEHP for 13 weeks. We identified 51 DEHP-regulated genes; these genes are involved in, but not limited to, peroxisome proliferation, xenobiotic detoxification, oxidative stress response, immune function, steroid hormone metabolism, testis development, and pheromone transport. The reproductive toxicity mechanism of DEHP may be due to its effects on steroid hormone metabolism and sexual development. Confirmation of microarray results with Northern blots demonstrated that both low- and high-dose DEHP treatments altered the expression of genes associated with testis development and steroid hormone synthesis. Vanin-1, a regulator of testis development, was upregulated after exposure to 0.2 and 1.0% DEHP by 1.8- and 2.9-fold, respectively. Several genes involved in hormone metabolism were also regulated by DEHP. 11betaHSDI was downregulated 1.8- and 3.1-fold by 0.2 and 1.0% DEHP, respectively, while HSD3b5 was suppressed similarly by 0.2% DEHP, 1.5-fold, and more severely by 1.0% DEHP, 8.0-fold. Interestingly, food restriction had a similar effect to DEHP on several genes, including HSD3b5. In addition, steroidogenic gene cyp7B1 was downregulated while phospholipid transfer protein and cyp2B9 were induced. Genes peripherally associated with steroid hormones were also affected: ALDH3, GSTtheta2, and Id2. Collectively, our data validate the concern for DEHP as a reproductive developmental toxicant"
Keywords:		"11-beta-Hydroxysteroid Dehydrogenases Amidohydrolases Animals Aryl Hydrocarbon Hydroxylases/metabolism Blotting, Northern Carrier Proteins/metabolism Cell Adhesion Molecules/biosynthesis/genetics Cytochrome P-450 Enzyme System/metabolism Cytochrome P450 F;neuroscience;"
Notes:		"MedlineWong, Jean S Gill, Sarjeet S eng Research Support, Non-U.S. Gov't 2002/12/25 Toxicol Appl Pharmacol. 2002 Dec 15; 185(3):180-96. doi: 10.1006/taap.2002.9540"