Different global gene expression profiles in benzo[a]pyrene-and dioxin-treated vascular smooth muscle cells of AHR-knockout and wild-type mice

Author: Karyala Saikumar   Guo Junhai   Sartor Maureen   Medvedovic Mario   Puga Alvaro   Ryan Patrick   Tomlinson Craig  

Publisher: Humana Press, Inc

ISSN: 1530-7905

Source: Cardiovascular Toxicology, Vol.4, Iss.1, 2004-03, pp. : 47-73

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Abstract

Benzo[a]pyrene (B[a]P) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are potent ligands for the aryl hydrocarbon receptor (AHR). High-density oligonucleotide microarrays were used to generate global gene expression profiles of wild-type and Ahr −/− vascular smooth muscle cells (SMCs) from mouse aorta. To determine whether there are signaling pathways other than the AHR involved in B[a]P metabolism, wild-type and AHR knockout (Ahr −/− SMCs were exposed to B[a]P. Two signaling pathways, represented by TGF-β2 and IGF-1, were identified as potential candidates of an AHR alternate pathway for cells to respond to B[a]P. The wild-type SMCs responded similarly to B[a]P and TCDD in the regulation of a small set of common genes known to respond to the activated AHR (e.g., glutamine S-transferase). However, wild-type SMCs responded in a way that involves many additional genes, suggesting that a very divergent cellular response may be involved when SMCs are exposed to the two classic inducers of the AHR. In contrast, many more genes in the Ahr −/− cells responded similarly to B[a]P and TCDD, inducluding Cyp1b1, than responded differently, which indicates that eliminating the AHR is effective for investigating potential alternate cellular mechanisms that respond to B[a]P and TCDD.

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