Ah Receptor: Involvement in Toxic Responses

2005 ◽  
pp. 491-532 ◽  
Author(s):  
Thomas A. Gasiewicz ◽  
Sang-Ki Park
Keyword(s):  
Ah Receptor ◽  
Toxic Responses

Ah receptor: Dioxin-mediated toxic responses as hints to deregulated physiologic functions

2006 ◽  
Vol 72 (4) ◽  
pp. 393-404 ◽  
Author(s):  
Karl Walter Bock ◽  
Christoph Köhle
Keyword(s):  
Ah Receptor ◽  
Toxic Responses

To TEF or not to TEF? That is the question

1994 ◽  
Vol 13 (8) ◽  
pp. 576-577
Author(s):  
J. Battershill
Keyword(s):  
Risk Assessment ◽  
Signal Transduction Pathway ◽  
Quantitative Information ◽  
Tumor Promoter ◽  
Laboratory Animals ◽  
Ah Receptor ◽  
Coplanar Pcbs ◽  
Structure Activity ◽  
The Individual ◽  
Toxic Responses

Commercial polychlorinated biphenyls (PCBs) and environmental extracts contain complex mixtures of congeners that can be unequivocally identified and quantitated. Some PCB mixtures elicit a spectrum of biochemical and toxic responses in humans and laboratory animals and many of these effects resemble those caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related halogenated aromatic hydrocarbons, which act through the aryl hydrocarbon (Ah)-receptor signal transduction pathway. Structure-activity relationships developed for PCB congeners and metabolites have demonstrated that several structural classes for compounds exhibit diverse biochemical and toxic responses. Structure-toxicity studies suggest that the coplanar PCBs, namely, 3,3',4,4'-tetrachlorobiphenyl (tetraCB). 3,3',4,4',5-pentaCB, 3,3',4,4',5,5'hexaCB, and their monoortho analogs are AH-receptor agonists and contribute significantly to the toxicity of the PCB mixtures. Previous studies with TCDD and structurally related compounds have utilized a toxic equivalency factor (TEF) approach for the hazard and risk assessment of polychlorinated dibenzo-p dioxin (PCDD) and polychlorinated dibenzofuran (PCDF) congeners in which the TCDD or toxic TEQ = Σ([PCDFi X TEFi]n) + Σ([PCDDi x TEFi] n) equivalent (TEQ) of a mixture is related to the TEFs and concentrations of the individual (i) congeners as indicated in the equation (note: n = the number of congeners). Based on the results of quantitative structure-activity studies, the following TEF values have been estimated by making use of the data available for the coplanar and mono-ortho coplanar PCBs: 3,3',4,4'5-pentaCB,0.1; 3,3',4,4',5,5'-hexaCB,0.05 ; 3,3',4,4'-tetraCB,0.01; 2,3,3',4,4'-pentaCB,0.001 ; 2,3,4,4',5-pentaCB, 0.0001; 2,3,3',4,4',5-hexaCB,0.0003 ; 2,3,3',4,4',5'-hexaCB,0.0003; 2',3,4, 4',5-pentaCB,0.00005; and 2,3,4,4',5-pentaCB, 0.0002. Application of the TEF approach for the risk assessment of PCBs must be used with considerable caution. Analysis of the results of laboratory animal and wildlife studies suggests that the predictive value of TEQs for PCBs may be both species-and response-dependent because both additive and non-additive (antagonistic) interactions have been observed with PCB mixtures. In the latter case, the TEF approach would significantly overestimate the toxicity of a PCB mixture. Analysis of the rodent carcinogenicity data for assessment of PCB mixtures that uses cancer as the endpoint cannot solely utilize a TEF approach and requires more quantitative information on the individual congeners contributing to the tumor-promoter activity of PCB mixtures.

The AH Receptor and a Novel Gene Determine Acute Toxic Responses to TCDD: Segregation of the Resistant Alleles to Different Rat Lines

1999 ◽  
Vol 155 (1) ◽  
pp. 71-81 ◽  
Author(s):  
Jouni T. Tuomisto ◽  
Matti Viluksela ◽  
Raimo Pohjanvirta ◽  
Jouko Tuomisto
Keyword(s):  
Ah Receptor ◽  
Novel Gene ◽  
Toxic Responses ◽  
Acute Toxic

Acetaminophen: Macula densa hypersecretory activity by induced hepatotoxicity

1987 ◽  
Vol 45 ◽  
pp. 934-935
Author(s):  
S.S. Poolsawat ◽  
C.A. Huerta ◽  
S.TY. Lae ◽  
G.A. Miranda
Keyword(s):  
Cell Proliferation ◽  
Liver Function ◽  
Chronic Inflammation ◽  
Foam Cell ◽  
Term Effect ◽  
Short Term ◽  
Drug Induced ◽  
Experimental Induction ◽  
Tissue Alterations ◽  
Toxic Responses

Introduction. Experimental induction of altered histology by chemical toxins is of particular importance if its outcome resembles histopathological phenomena. Hepatotoxic drugs and chemicals are agents that can be converted by the liver into various metabolites which consequently evoke toxic responses. Very often, these drugs are intentionally administered to resolve an illness unrelated to liver function. Because of hepatic detoxification, the resulting metabolites are suggested to be integrated into the macromolecular processes of liver function and cause an array of cellular and tissue alterations, such as increased cytoplasmic lysis, centrilobular and localized necroses, chronic inflammation and “foam cell” proliferation of the hepatic sinusoids (1-4).Most experimentally drug-induced toxicity studies have concentrated primarily on the hepatic response, frequently overlooking other physiological phenomena which are directly related to liver function. Categorically, many studies have been short-term effect investigations which seldom have followed up the complications to other tissues and organs when the liver has failed to function normally.

scholarly journals THE Ah PHENOTYPE. SURVEY OF FORTY-EIGHT RAT STRAINS AND TWENTY INBRED MOUSE STRAINS

Genetics ◽  
1982 ◽  
Vol 100 (1) ◽  
pp. 79-87
Author(s):  
Daniel W Nebert ◽  
Nancy M Jensen ◽  
Hisashi Shinozuka ◽  
Heinz W Kunz ◽  
Thomas J Gill
Keyword(s):  
Specific Activity ◽  
Inbred Mouse ◽  
Inbred Mouse Strain ◽  
Mouse Strains ◽  
Ah Receptor ◽  
Inbred Mouse Strains ◽  
Sprague Dawley ◽  
Rat Strains ◽  
Specific Activities ◽  
Inbred Rat

ABSTRACT Forty-four inbred and four randombred rat strains and 20 inbred mouse strains were examined for their Ah phenotype by determining the induction of liver microsomal aryl hydrocarbon (benzo[a]pyrene) hydroxylase activity (EC 1.14.14.1) by intraperitoneal treatment with either β-naphthoflavone or 3-methylcholanthrene. All 48 rat strains were found to be Ah-responsive. The maximally induced hydroxylase specific activities of the ALB/Pit, MNR/Pit, MR/Pit, SHR/Pit, and Sprague-Dawley strains were of the same order of magnitude as the basal hydroxylase specific activities of the ACI/Pit, F344/Pit, OKA/Pit, and MNR/N strains. Six of the 20 mouse strains were Ah-nonresponsive (i.e. lacking the normal induction response and presumably lacking detectable amounts of the Ah receptor). The basal hydroxylase specific activities of the BDL/N, NFS/N, STAR/N, and ST/JN mouse strains were more than twice as high as the maximally induced hydroxylase specific activity of the CBA/HT strain.——To date, 24 Ah-nonresponsive mouse strains have been identified, out of a total of 68 known to have been characterized. The reasons for not finding a single Ah-nonresponsive inbred rat strain—as compared with about one Ah-nonresponsive inbred mouse strain found for every three examined—remain unknown.

scholarly journals Photoaffinity labeling of the nuclear Ah receptor from mouse Hepa 1c1c7 cells using 2,3,7,8-[3H]tetrachlorodibenzo-p-dioxin

1989 ◽  
Vol 264 (31) ◽  
pp. 18463-18471
Author(s):  
J P Landers ◽  
J Piskorska-Pliszczynska ◽  
T Zacharewski ◽  
N J Bunce ◽  
S Safe
Keyword(s):  
Photoaffinity Labeling ◽  
Ah Receptor ◽  
Tetrachlorodibenzo P Dioxin
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