Different global gene expression profiles in benzo[a]pyrene- and dioxin-treated vascular smooth muscle cells of AHR-knockout and wild-type mice.
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.
Karyala
Saikumar
S
Department of Environmental Health and Center for Environmental Genetics, Division of Toxicology, University of Cincinnati, Cincinnati, OH 45267-0056, USA.
Guo
Junhai
J
Sartor
Maureen
M
Medvedovic
Mario
M
Kann
Simone
S
Puga
Alvaro
A
Ryan
Patrick
P
Tomlinson
Craig R
CR
D000818:Animals; D001011:Aorta / Q000187:drug effects; D001564:Benzo(a)pyrene / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D002478:Cells, Cultured; D004147:Dioxins / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects*; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D020411:Oligonucleotide Array Sequence Analysis; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002273:Carcinogens; D004147:Dioxins; D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D001564:Benzo(a)pyrene