Document Detail


The structure-dependent effects of heptachlorodibenzofuran isomers in male C57BL/6 mice: immunotoxicity and monooxygenase enzyme induction.
MedLine Citation:
PMID:  2227157     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The dose-response effects of the 1,2,3,4,6,7,8-, 1,2,3,4,7,8,9-, 1,2,3,4,6,8,9-, and 1,2,3,4,6,7,9-heptachlorodibenzofurans (HpCDFs) on the splenic plaque-forming cell (PFC) response to sheep erythrocytes and on the induction of hepatic microsomal aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin-O-deethylase (EROD) activities were determined in male C57BL/6 mice. The ED50 values for the decrease in the PFCs/spleen, the number of PFCs/10(6) viable cells, and the induction of AHH and EROD activities were 1,2,3,4,6,7,8-HpCDF, 0.011, 0.018, 0.11, and 0.315 mumol/kg, respectively; 1,2,3,4,7,8,9-HpCDF, 0.012, 0.054, 0.70, and 0.20 mumol/kg, respectively; 1,2,3,4,6,7,9-HpCDF, 1.2, 1.3, greater than 43, and greater than 43 mumol/kg, respectively; 1,2,3,4,6,8,9-HpCDF, 1.5, 3.4, 22, and 22 mumol/kg, respectively. It was apparent from these studies that the 2,3,7,8-substituted HpCDF isomers (1,2,3,4,6,7,8- and 1,2,3,4,7,8,9-) were significantly more potent than the compounds which contained only three lateral C1 groups. These results were obtained using a multiple dosing regimen in which 10 separate doses of the HpCDF isomers were administered to the mice by intraperitoneal injection over a period of 12 days. However, when the mice were treated with a single dose of an HpCDF congener, which was equivalent to the total dose used in the multiple dose study, the responses were comparable. A comparison of the relative immunotoxic potencies of the 2,3,7,8-substituted HpCDFs and 2,3,7,8-tetrachlorodibenzo-p-dioxin showed that the latter compound was approximately 10 times more active than the HpCDFs.
Authors:
R Dickerson; L Howie; D Davis; S Safe
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Fundamental and applied toxicology : official journal of the Society of Toxicology     Volume:  15     ISSN:  0272-0590     ISO Abbreviation:  Fundam Appl Toxicol     Publication Date:  1990 Aug 
Date Detail:
Created Date:  1990-12-05     Completed Date:  1990-12-05     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8200838     Medline TA:  Fundam Appl Toxicol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  298-307     Citation Subset:  IM    
Affiliation:
Department of Veterinary Physiology & Pharmacology, Texas A&M University, College Station 77843.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibody Formation / drug effects
Benzofurans / toxicity*
Cytochrome P-450 Enzyme System / biosynthesis
Enzyme Induction / drug effects
Immunity / drug effects*
Isomerism
Male
Mice
Mice, Inbred C57BL
Mixed Function Oxygenases / biosynthesis*
Sheep / immunology
Spleen / cytology,  immunology
Structure-Activity Relationship
Grant Support
ID/Acronym/Agency:
P42-ES04917/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Benzofurans; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.-/Mixed Function Oxygenases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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