Document Detail


Characterization of mutagenic glucuronide formation from benzo(a)pyrene in the nonrecirculating perfused rat liver.
MedLine Citation:
PMID:  6488167     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Excretion of mutagenic metabolites of benzo(a)pyrene into bile from livers of corn oil- or 3-methylcholanthrene-treated Sprague-Dawley rats perfused with a nonrecirculating perfusion system was quantitated. Mutagenic benzo(a)pyrene metabolites were detected using Salmonella typhimurium (strain TA 98) grown in the presence of limiting amounts of histidine. Microsomes were not included in the bacterial assay since metabolic activation was carried out by the perfused liver. Mutagenic activity was detected only if beta-glucuronidase was added to the assay mixture or if bile was treated with acid to hydrolyze glucuronides prior to assay. When livers were perfused with 20 microM benzo(a)pyrene, stable, mutagenic glucuronides were exported from corn oil-treated livers at maximal rates of 149 +/- 24 (S.E.) revertants/g/hr and at rates of 225 +/- 22 revertants/g/hr in livers from 3-methylcholanthrene-treated rats. Chromatography of bile by high-performance liquid chromatography demonstrated that two peak areas contained phenolic glucuronides which were hydrolyzed by beta-glucuronidase. These two peaks, one which cochromatographed with authentic 3-benzo(a)pyrenyl-beta-D-glucuronide, accounted for all of the mutagenic activity in bile from livers perfused with benzo(a)pyrene. A good correlation (r = 0.86) between rates of mutagen production and rates of formation of phenolic glucuronides was observed under a variety of experimental conditions. The mutagenic activity observed with pure 3-benzo(a)pyrenyl-beta-D-glucuronide exposed to beta-glucuronidase was 4 revertants/nmol. When the rate of mutagen production was divided by the rate of production of 3-benzo(a)pyrenyl-beta-D-glucuronide by the perfused liver, a value of 4 revertants/nmol was also obtained. Therefore, it is concluded that mutagens exported in bile from livers perfused with benzo(a)pyrene can be accounted for predominantly by hydrolysis products of phenolic glucuronides.
Authors:
F W Kari; F C Kauffman; R G Thurman
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cancer research     Volume:  44     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  1984 Nov 
Date Detail:
Created Date:  1984-11-28     Completed Date:  1984-11-28     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  5073-8     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Benzo(a)pyrene / metabolism*
Benzopyrenes / isolation & purification,  metabolism*
Bile / analysis
Biotransformation
Chromatography, High Pressure Liquid
Female
Glucuronidase / metabolism
Kinetics
Liver / metabolism*
Mutagens / metabolism*
Perfusion
Rats
Rats, Inbred Strains
Sulfatases / metabolism
Grant Support
ID/Acronym/Agency:
AA-00033/AA/NIAAA NIH HHS; CA-20807/CA/NCI NIH HHS; CA-23080/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Benzopyrenes; 0/Mutagens; 50-32-8/Benzo(a)pyrene; 60262-81-9/benzo(a)pyrene-3-O-glucuronide; EC 3.1.6.-/Sulfatases; EC 3.2.1.31/Glucuronidase

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


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