Different Global Gene Expression Profiles in Benzo[a]Pyrene- and Dioxin-Treated Vascular Smooth Muscle Cells of AHR-Knockout and Wild-Type Mice

被引：43

作者：

Karyala S. ^{[1
]}

Guo J. ^{[2
]}

Sartor M. ^{[2
]}

Medvedovic M. ^{[2
,3
]}

Kann S. ^{[1
]}

Puga A. ^{[1
]}

Ryan P. ^{[2
]}

Tomlinson C.R. ^{[1
,4
]}

机构：

[1] Department of Environmental Health, Center for Environmental Genetics, University of Cincinnati, Cincinnati, OH

[2] Div. of Biostatist. and Epidemiology, University of Cincinnati, Cincinnati, OH

[3] Center for Genome Information, University of Cincinnati, Cincinnati, OH

[4] Center for Environmental Genetics, Kettering Lab. 334, University of Cincinnati, Cincinnati, OH 45267-0056

来源：

Cardiovascular Toxicology | 2004年 / 4卷 / 1期

关键词：

Aryl hydrocarbon receptor; Benzo [a]pyrene; Dioxin; aorta; Gene expression profiles; Microarrays; Mouse smooth muscle cells; Transforming growth factor-β;

D O I：

10.1385/CT:4:1:47

中图分类号：

学科分类号：

摘要：

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, 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.

引用

页码：47 / 73

页数：26

共 39 条

[1]

Gelboin H.V., Benzo[a]pyrene metabolism, activation and carcinogenesis: Role and regulation of mixed-function oxidases and related enzymes, Physiol. Rev., 60, pp. 1107-1066, (1980)

[2]

Ramos K.S., Redox regulation of c-Ha-ras and osteopontin signaling in vascular smooth muscle cells. Implications in chemical atherogenesis, Annu. Rev. Pharmacol. Toxicol., 29, pp. 243-265, (1999)

[3]

Birnbaum L.S., The mechanism of dioxin toxicity: Relationship to risk assessment, Environ. Health Perspect., 102, SUPPL. 9, pp. 157-167, (1994)

[4]

Nebert D.W., Puga A., Vasiliou V., Role of the Ah receptor and the dioxin-inducible [Ah] gene battery in toxicity, cancer, and signal transduction, Ann. NY Acad. Sci., 685, pp. 624-640, (1993)

[5]

Sayer J.M., Whalen D.L., Jerina D.M., Chemical strategies for the inactivation of bay-region diolepoxides, ultimate carcinogens derived from polycyclic aromatic hydrocarbons, Drug Metab. Rev., 20, pp. 155-182, (1989)

[6]

Denissenko M.F., Pao A., Tang M., Pfeifer G.P., Preferential formation of benzo[a]pyrene adducts at lung cancer mutational hot spots in P53, Science, 274, pp. 430-432, (1996)

[7]

Landers J.P., Bunce N.J., The Ah receptor and the mechanism of dioxin toxicity, Biochem. J., 276, pp. 273-287, (1991)

[8]

Fernandez-Salguero P., Pineau T., Hilbert D.M., McPhail T., Lee S.S., Kimura S., Nebert D.W., Rudikoff S., Ward J.M., Gonzalez F.J., Immune system impairment and hepatic fibrosis in mice lacking the dioxin-binding Ah receptor, Science, 268, pp. 722-726, (1995)

[9]

Brenner D.A., New functions for the aryl hydrocarbon receptor, Hepatology, 23, pp. 379-380, (1996)

[10]

Schmidt J.V., Su G.H.-T., Reddy J.K., Simon M.C., Bradfield C.A., Characterization of a murine Ahr null allele: Involvement of the Ah receptor in hepatic growth and development, Proc. Natl. Acad. Sci. USA, 93, pp. 6731-6736, (1996)

← 1 2 3 4 →