The AH Receptor in Biology and Toxicology

The complete guide to the aryl hydrocarbon receptor(AHR) what it is, what it does, and what it might mean for thefuture of drug metabolism

Providing a thorough and up–to–date overview of the arylhydrocarbon receptor (AHR), a ligand–activated transcription factorthat mediates the induction of drug–metabolizing enzymes anddiverse toxicities caused by dioxins, The AH Receptor in Biologyand Toxicology is essential reading for toxicologists, chemists,biologists, pharmacologists, and other experts studying drugmetabolism.

Evidence suggests that the AHR protein imparts importantphysiological functions that place it at the crossroad of biologyand toxicology, making it the focus of extensive research activity.Examining the unique dual role of AHR as both a toxicant and afactor in biological processes, this comprehensive reference workcovers the full spectrum of AHR topics from basic concepts,toxicological risk analysis, and models, to polymorphisms andrelated diseases. Addressing epigenetic mechanisms, geneexpression, reproductive/developmental toxicity, signaltransduction, and transgenic animal models, the book runs the gamutof AHR knowledge.

With contributions from renowned international experts, The AHReceptor in Biology and Toxicology puts the forefront of AHRresearch at your fingertips.

A. Historical background.

1. History of Research on the AHR (Thomas A. Gasiewocz andEllen C. Henry).

B. AHR as a ligand–activated transcription factor.

2. Overview of AHR functional domains and the classicalsignaling pathway: induction of drug–metabolizing enzymes (QiangMa).

3. Role of chaperone proteins in AHR function (Iain A. Murrayand Gary H. Perdew).

4. AHR Ligands: Promiscuity in Binding and Diversity in Response(Danica DeGroot, Guochun He, Domenico Fraccalvieri, LauraBonati, Allesandro Pandin and Michael S. Denison).

5. Dioxin response elements and regulation of gene transcription(Hollie Swanson).

6. The AHR/ARNT dimer and transcriptional coactivators(Oliver Hankinson).

7. Regulation of AHR by the AHR repressor (AHRR) (YoshiakiFujii–Kuriyama and Kaname Kawajiri).

8. Influence of HIF–1 and Nrf2 signaling on AHR–mediatedgene expression, toxicity and biological functions (ThomasHaarmann–Stemmann and Josef Abel).

9. Functional interactions of AHR with other receptors (SaraBrunnberg, Elin Swedenborg and Jan–Åke Gustafsson).

10. The E3 ubiquitin ligase activity of transcription factor AHRpermits non–genomic regulation of biological pathways (FumiakiOhtake and Shigeaki Kato).

11. Epigenetic mechanisms in AHR function (Chia–I Ko andAlvaro Puga).

C. AHR as a mediator of xenobiotic toxicities: dioxins as akey example.

12. Role of the AHR and its structure in TCDD toxicity (RaimoPohjanvirta, Merja Korkalainen, Ivy D. Moffat, Paul C. Boutros,Allan B. Okey).

13. Nongenomic route of action of TCDD: Identity,characteristics and toxicological significance (FumioMatsumura).

14. Inter–species heterogeneity in the hepatic transcriptomicresponse to AHR activation by dioxin (Paul Boutros).

15. Dioxin–activated AHR: toxic responses and the induction ofoxidative stress (Sidney J. Stohs and Ezdihar A.Hassoun).

16. Dioxin–activated AHR and cancer in laboratory animals(Dieter Schrenk and Martin Chopra).

17. Teratogenic impact of dioxin–activated AHR in laboratoryanimals (Barbara D. Abbott).

18. The developmental toxicity of dioxin to the developing malereproductive system in the rat; relevance of the AHR for riskassessment (David R. Bell).

19. TCDD, AHR and immune regulation (Nancy I.Kerkvliet).

20. Effects of dioxins on teeth and bone: the role of AHR(Matti Viluksela, Hanna M. Miettinen and MerjaKorkalainen).

21. Impacts of dioxin–activated AHR signaling in fish and birds(Michael T. Simonich and Robert L. Tangray).

22. Adverse Health Outcomes Caused By Dioxin–Activated AHR inHumans (Sally S. White, Suzanne E. Fenton, and Linda S.Birnbaum).

23. The toxic equivalency principle and its application indioxin risk assessment (Jouko Tuomisto).

24. AHR–active compounds in the human diet (Stephen Safe,Gayathri Chadalapaka and Indira Jutooru).

25. Modulation of AHR function by heavy metals and diseasestates (Anwar Anwar–Mohammed and Ayman O.S. El–Kadi).

26. Transgenic mice with a constitutively active AHR: a modelfor human exposure to dioxin an other AHR ligands (PatrikAndersson, Sara Brunnberg, Carolina Wejheden, Lorenz Poellinger andAnnika Hanberg).

D. AHR as a physiological regulator.

27. Structural and functional diversification of AHRs duringmetazoan evolution (Mark E. Hahn and Sibel I. Karchner).

28. Invertebrate AHR homologs: Ancestral functions in sensorysystems (Jo Anne Powell–Coffman and Hongtao Qin).

29. Role of AHR in the development of the liver and bloodvessels (Sahoko Ichihara).

30. Involvement of the AHR in cardiac function and regulation ofblood pressure (Jason A. Scott and Mary K. Walker).

31. Involvement of the AHR in development and functioning of thefemale and male reproductive systems (Bethany N. Karman, IsabelHernández–Ochoa, Ayelet Ziv–Gal, Jodi A. Flaws).

32. The AHR in the control of cell cycle and apoptosis(Cornelia Dietrich).

33. The AHR regulates cell adhesion and migration by interactingwith oncogene and growth factor–dependent signaling (AngelCarlos Roman, Jose M. Carvajal–Gonzalez, Sonia Mulero–Navarro,Aurea Gomez–Duran, Eva M. Rico–Leo and Pedro M.Fernandez–Salguero).

34. The physiological role of AHR in the mouse immune system(Charlotte Esser).

35. AHR and the circadian clock (Shelley A.Tischkau). 

Raimo Pohjanvirta, PhD, is Professor of Toxicology at theUniversity of Helsinki. He has been studying the effects and actionmechanisms of dioxins for over twenty years, publishing over ahundred peer–reviewed papers on dioxins and AHR. Dr. Pohjanvirtahas been an invited lecturer at major international conferences,including the Society of Toxicology, EUROTOX, and the BritishToxicology Society.