Document Detail


Mutagenicity of bisphenol A (4,4'-isopropylidenediphenol) in vitro: effects of nitrosylation.
MedLine Citation:
PMID:  12395404     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Bisphenol A (4,4'-isopropylidenediphenol) is a common component of polycarbonate plastics and epoxy resins. Since bisphenol A-containing plastics and resins have found uses in food-contact items, its potential migration into foodstuffs and possible health consequences have been the focus of many recent studies. However, the potential mutagenic activation of bisphenol A by nitrosylation has received little attention. Incubation of bisphenol A with sodium nitrite under acidic conditions produced a yellow-brown product. When nitrosylated bisphenol A was tested in the Ames Salmonella/microsome assay at 100 ng to 1 mg/plate, dose-dependent increases in mutagenicity were found in both TA98 and TA100 Salmonella strains. These results indicated the presence of a direct-acting mutagenic activity causing both frameshift and base pair mutations, respectively. When compared to colony formation in untreated controls, the addition of rat liver S9 for metabolic activation had little influence on revertant colony formation. Unreacted bisphenol A dissolved in DMSO, acidic buffer, or inactivated nitrosylation solution showed negligible mutagenicity. When the nature of the mutagenic changes was examined using the Ames II trade mark Assay, a variety of base pair changes was found including T:A to A:T - S9, G:C to A:T +/- S9,C:G to A:T +/- S9 and C:G to G:C +/- S9. Bisphenol A also induced frameshift mutations at G:C sites. In addition, the presence of electrophiles was shown by the production of an intensely coloured orange-red product upon incubation of nitrosylated bisphenol A with the nucleophile 4-(4'-nitrobenzyl)pyridine. These findings suggest that migration of bisphenol A into nitrite containing foodstuffs, or its ingestion in the presence of nitrite, could lead to the formation of mutagenic compounds.
Authors:
Timothy J Schrader; I Langlois; K Soper; W Cherry
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Teratogenesis, carcinogenesis, and mutagenesis     Volume:  22     ISSN:  0270-3211     ISO Abbreviation:  Teratog., Carcinog. Mutagen.     Publication Date:  2002  
Date Detail:
Created Date:  2002-10-23     Completed Date:  2003-05-13     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  8100917     Medline TA:  Teratog Carcinog Mutagen     Country:  United States    
Other Details:
Languages:  eng     Pagination:  425-41     Citation Subset:  IM    
Affiliation:
Toxicology Research Division, Food Directorate, Health Canada, Banting Research Centre,Tunney's Pasture, Ottawa, Ontario, Canada. Tim_Schrader@hc-sc.gc.ca
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MeSH Terms
Descriptor/Qualifier:
Air Pollutants, Occupational / toxicity*
Animals
DNA / drug effects*
Frameshift Mutation
Indicators and Reagents / pharmacology
Liver / metabolism
Male
Models, Chemical
Mutagenicity Tests
Mutagens*
Phenols / toxicity*
Pyridines / pharmacology
Rats
Rats, Sprague-Dawley
Salmonella / drug effects,  genetics
Sodium Nitrite / pharmacology
Chemical
Reg. No./Substance:
0/Air Pollutants, Occupational; 0/Indicators and Reagents; 0/Mutagens; 0/Phenols; 0/Pyridines; 1083-48-3/4-(4-nitrobenzyl)pyridine; 7632-00-0/Sodium Nitrite; 80-05-7/bisphenol A; 9007-49-2/DNA

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


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