Ah Receptor Binding

The geometries of all conformations were optimized by the PM3 Hamiltonian. A poor correlation between AhR binding and Slumo was found (r = 0.38) when all 

Similar results were obtained for nonoptimized conformers whose electronic structure was assessed by single point (ISCF) calculations. The selection of the most planar conformers yielded again a significant QSAR model, = 0.78. 

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Tributyltins and other organotins induce chromosomal aberrations in mammals, although this was not observed in tests with aquatic invertebrates (Dixon and Prosser 1986). Studies with isolated rat hepatoma cells, TBT, and PCB 126, show that TBT inhibits cytochrome P-4501A activity, and PCB 126 induces EROD activity. However, PCB-induced EROD activity was potentiated by coexposure to low noncytotoxic concentrations of TBT (Kannan et al. 1998b). Authors concluded that TBT does not interfere with Ah receptor binding and that potentiation of EROD activity and cytotoxicity as a result of coexposure to PCB 126 and TBT is significant because they coaccumulated in a variety of marine organisms. 

Mekenyan, O.G., Veith, G.D., Call, D.J. andAnkley, G.T. (1996) AQSARevaluation of Ah receptor binding of haloginated aromatic zenobiotiocs. Environmental Health Perspectives, 104, 1302-1310. 

Mekenyan, O.G. et al. (1996) A QSAR evaluation of Ah receptor binding of halogenated aromatic xenobiotics. Environ. Health Perspect., 104 (12), 1302-1310. 

Sloop TC, Lucier GW. 1987. Dose-dependent elevation of Ah receptor binding by TCDD rat liver. Toxicol Appl Pharmacol 88 329-337. 

Quattrochi LC, Vu T, Tukey RH. The human CYP1A2 gene and induction by 3-methylcholanthrene. A region of DNA that supports AH-receptor binding and promoter-specific induction. J Biol Chem 1994 269 6949-6954. 

Since the toxicology data on PCDEs is still limited, PCDEs should be considered as compounds having possible adverse effects on wildlife and humans until more data is provided. PCDEs have shown low toxic potency in fish, but this is also true for PCBs, some of which are quite toxic in mammals. Mono-ortho-PCBs have not caused rainbow trout early life stage mortality and non-ortho-PCBs have shown unexpectedly low early life stage mortality when comparing Ah-receptor binding affinities in mammals [144],... 

Tuppurainen K, Ruuskanen J. 2000. Electronic eigenvalue (LEVA) a new QSAR/QSPR descriptor for electronic substituent effects based on molecular orbital energies. A QSAR approach to the Ah receptor binding affinity of polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs). Chemosphere 41 843 48... 

Jellinck PH, Forkert PG, Riddick DS, Okey AB, Michnovicz JJ, Bradlow HL. 1993. Ah receptor binding properties of indole carbinols and induction of hepatic estradiol hydroxylation. Biochem. Pharmacol. 45 1129-36... 

Zheng G, Xiao M, Lu XH. QSAR study on the Ah receptor-binding affinities of polyhalogenated dibenzo-p-dioxins using net atomic-charge descriptors and a radial basis neural network. Anal Bioanal Chem 2005 383 810-6. 

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