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. 2004;4(1):47-73. doi: 10.1385/ct:4:1:47.


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-beta2 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, including 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Aorta / drug effects
  • Benzo(a)pyrene / toxicity*
  • Carcinogens / toxicity*
  • Cells, Cultured
  • Dioxins / toxicity*
  • Environmental Pollutants / toxicity*
  • Gene Expression Regulation / drug effects*
  • Mice
  • Mice, Knockout
  • Muscle, Smooth, Vascular / drug effects*
  • Oligonucleotide Array Sequence Analysis
  • Polychlorinated Dibenzodioxins / toxicity
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • RNA, Messenger / isolation & purification
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction


  • Carcinogens
  • Dioxins
  • Environmental Pollutants
  • Polychlorinated Dibenzodioxins
  • RNA, Messenger
  • Receptors, Aryl Hydrocarbon
  • Benzo(a)pyrene