Skip Navigation



ToxSci Advance Access published online on August 8, 2007
Toxicological Sciences, doi:10.1093/toxsci/kfm207
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
100/1/180    most recent
kfm207v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Jönsson, M. E.
Right arrow Articles by Stegeman, J. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jönsson, M. E.
Right arrow Articles by Stegeman, J. J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2007. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Role of AHR2 in the Expression of Novel Cytochrome P450 1 Family Genes, Cell Cycle Genes, and Morphological Defects in Developing Zebrafish Exposed to 3,3',4,4',5-pentachlorobiphenyl or 2,3,7,8-tetrachlorodibenzo-p-dioxin

Maria E. Jönsson*,{dagger}, Matthew J. Jenny*, Bruce R. Woodin*, Mark E. Hahn* and John J. Stegeman*

* Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA 02543, USA {dagger} Department of Environmental Toxicology, Uppsala University, Norbyvägen 18A, SE-752 36 Uppsala, Sweden (Current Address)

Address for correspondence: Department of Environmental Toxicology, Uppsala University, Norbyvägen 18A, SE-752 36 Uppsala, Sweden, mjonsson{at}whoi.edu, phone: +46 18 471 26 25, fax: +46 18 51 88 43

Received May 26, 2007; revision received July 28, 2007; accepted July 30, 2007


  Abstract

Halogenated agonists for the aryl hydrocarbon receptor (AHR), such as 3,3',4,4',5-pentachlorobiphenyl (PCB126) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), cause developmental toxicity in fish. AHR-dependence of these effects is known for TCDD but only presumed for PCB126, and the AHR-regulated genes involved are known only in part. We defined the role of AHR in regulation of four cytochrome P450 1 (CYP1) genes, and the effect of PCB126 on cell cycle genes (i.e., PCNA and cyclin E) in zebrafish (Danio rerio) embryos. Basal and PCB126-induced expression of CYP1A, CYP1B1, CYP1C1, and CYP1C2 was examined over time as well as in relation to cell cycle gene expression and morphological effects of PCB126 in developing zebrafish. The four CYP1 genes differed in the time for maximal basal and induced expression, i.e., CYP1B1 peaked within 2 days post-fertilization (dpf), the CYP1Cs around hatching (3 dpf), and CYP1A after hatching (14–21 dpf). These results indicate developmental periods when the CYP1s may play physiological roles. PCB126 (0.3–100 nM) caused concentration-dependent CYP1 gene induction (EC50: 1.4–2.7 nM, LOEC: 0.3–1 nM) and pericardial edema (EC50: 4.4 nM, LOEC: 3 nM) in 3-dpf embryos. Blockage of AHR2 translation significantly inhibited these effects of PCB126 and TCDD. PCNA gene expression was reduced by PCB126 in a concentration-dependent manner, suggesting that PCB126 could suppress cell proliferation. Our results indicate that the four CYP1 genes examined are regulated by AHR2 and that the effect of PCB126 on morphology in zebrafish embryos is AHR2-dependent. Moreover, the developmental patterns of expression and induction suggest that CYP1 enzymes could function in normal development and in developmental toxicity of PCB126 in fish embryos.

Key Words: Cytochrome P450 1 (CYP1); 3,3',4,4',5-pentachlorobiphenyl (PCB126); 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); embryotoxicity; aryl hydrocarbon receptor (AHR); PCNA.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Toxicol SciHome page
M. J. Jenny, S. I. Karchner, D. G. Franks, B. R. Woodin, J. J. Stegeman, and M. E. Hahn
Distinct Roles of Two Zebrafish AHR Repressors (AHRRa and AHRRb) in Embryonic Development and Regulating the Response to 2,3,7,8-Tetrachlorodibenzo-p-dioxin
Toxicol. Sci., August 1, 2009; 110(2): 426 - 441.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
A. C. Grimes, K. N. Erwin, H. A. Stadt, G. L. Hunter, H. A. Gefroh, H.-J. Tsai, and M. L. Kirby
PCB126 Exposure Disrupts ZebraFish Ventricular and Branchial but Not Early Neural Crest Development
Toxicol. Sci., November 1, 2008; 106(1): 193 - 205.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
S. M. Billiard, J. N. Meyer, D. M. Wassenberg, P. V. Hodson, and R. T. Di Giulio
Nonadditive effects of PAHs on Early Vertebrate Development: mechanisms and implications for risk assessment
Toxicol. Sci., September 1, 2008; 105(1): 5 - 23.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
H.-C. Yin, H.-P. Tseng, H.-Y. Chung, C.-Y. Ko, W.-S. Tzou, D. R. Buhler, and C.-H. Hu
Influence of TCDD on Zebrafish CYP1B1 Transcription during Development
Toxicol. Sci., May 1, 2008; 103(1): 158 - 168.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
J. V. Goldstone, H. M. H. Goldstone, A. M. Morrison, A. Tarrant, S. E. Kern, B. R. Woodin, and J. J. Stegeman
Cytochrome P450 1 Genes in Early Deuterostomes (Tunicates and Sea Urchins) and Vertebrates (Chicken and Frog): Origin and Diversification of the CYP1 Gene Family
Mol. Biol. Evol., December 1, 2007; 24(12): 2619 - 2631.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.