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

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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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Authors and Affiliations

  1. Department of Environmental Health, Division of Toxicology, University of Cincinnati, Cincinnati, OH

    Saikumar Karyala, Alvaro Puga & Craig R. Tomlinson

  2. Division of Biostatistics and Epidemiology, University of Cincinnati, Cincinnati, OH

    Junhai Guo, Maureen Sartor, Mario Medvedovic & Patrick Ryan

  3. Center for Genome Information, University of Cincinnati, Cincinnati, OH

    Mario Medvedovic

  4. Center for Environmental Genetics, Division of Toxicology Kettering Lab 334, University of Cincinnati, 3223 Eden Avenue, 45267-0056, Cincinnati, OH

    Saikumar Karyala, Alvaro Puga & Craig R. Tomlinson

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  1. Saikumar Karyala
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  2. Junhai Guo
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Correspondence to Craig R. Tomlinson.

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Karyala, S., Guo, J., Sartor, M. et al. Different global gene expression profiles in benzo[a]pyrene-and dioxin-treated vascular smooth muscle cells of AHR-knockout and wild-type mice. Cardiovasc Toxicol 4, 47–73 (2004). https://doi.org/10.1385/CT:4:1:47

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  • DOI: https://doi.org/10.1385/CT:4:1:47

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