| Polybrominated dibenzo-p-dioxins and related compounds: quantitative in vivo and in vitro structure-activity relationships. | |
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MedLine Citation:
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PMID: 3033849 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The effects of structure on the in vitro receptor binding affinities, aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) induction potencies in rat hepatoma cells were determined for the following compounds: 2-bromo-, 2,7/2,8-dibromo-, 2,3,7-tribromo-, 2,4,6,8/1,3,7,9-tetrabromo-, 2,3,7,8-tetrabromo-, 1,3,7,8-tetrabromo-, 1,2,3,7,8-pentabromo-, 1,2,4,7,8-pentabromo-, 2,3-dibromo-7,8-dichloro-, 2,8-dibromo-3,7-dichloro- and 2-bromo-3,7,8-trichlorodibenzo-p-dioxin. The structure-activity relationships (SARs) for the polybrominated dibenzo-p-dioxins (PBDDs) were comparable for both in vitro responses: the most active compounds were substituted only in the lateral 2,3,7 and 8 position and the addition of non-lateral or removal of lateral halogen substituents reduced the activity of the resultant compound. The biologic and toxic effects of 2,3,7,8-tetrabromo-, 1,3,7,8-tetrabromo-, 1,2,4,7,8-pentabromo-1,2,3,7,8-pentabromo-, 2-bromo-3,7,8-trichloro- and 2,3-dibromo-7,8-dichlorodibenzo-p-dioxin on several receptor-mediated responses (thymic atrophy, body weight loss, hepatic microsomal AHH and EROD induction) were determined in a dose-response fashion in immature male Wistar rats. A comparison of the ED50 values for the in vivo responses demonstrated that the SARs for the PBDDs and brominated polychlorinated dibenzo-p-dioxins were comparable to those observed for in vitro receptor binding and AHH induction. Moreover, there was an excellent linear correlation between the -log EC50 (in vitro AHH induction) vs. the in vivo -log ED50 (thymic atrophy) and -log ED50 (body wt loss) correlation coefficient, r = 0.97 for all 2 correlations). |
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Authors:
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G Mason; T Zacharewski; M A Denomme; L Safe; S Safe |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Toxicology Volume: 44 ISSN: 0300-483X ISO Abbreviation: Toxicology Publication Date: 1987 Jun |
Date Detail:
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Created Date: 1987-06-01 Completed Date: 1987-06-01 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0361055 Medline TA: Toxicology Country: NETHERLANDS |
Other Details:
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Languages: eng Pagination: 245-55 Citation Subset: IM |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Aryl Hydrocarbon Hydroxylases / biosynthesis Cell Line Cytochrome P-450 CYP1A1 Dioxins / chemical synthesis, toxicity* Enzyme Induction / drug effects Hydrocarbons, Brominated / chemical synthesis, toxicity* Isomerism Liver / metabolism Male Oxidoreductases / biosynthesis Rats Rats, Inbred Strains Receptors, Aryl Hydrocarbon Receptors, Drug / metabolism Structure-Activity Relationship |
| Chemical | |
Reg. No./Substance:
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0/Dioxins; 0/Hydrocarbons, Brominated; 0/Receptors, Aryl Hydrocarbon; 0/Receptors, Drug; EC 1.-/Oxidoreductases; EC 1.14.14.1/Aryl Hydrocarbon Hydroxylases; EC 1.14.14.1/Cytochrome P-450 CYP1A1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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