Document Detail


Inability to confirm estrogenicity of the heterocyclic amine PhIP in two in vitro assays.
MedLine Citation:
PMID:  20036730     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
2-Amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine (PhIP) is a heterocyclic amine which is found in food after cooking and which is a known mutagen. Reports from several laboratories have proposed that PhIP has estrogenic activity, which would classify PhIP as a xenoestrogen with human exposure via food. We tested PhIP in two cell-based assays for estrogenicity, both based on human cell lines but utilising different outcome measures: ERLUX (reporter-gene activation) and ESCREEN (cell proliferation). PhIP was inactive in both assays at concentrations spanning the picomolar to micromolar range. To eliminate supplier differences as an explanation for the disparity between these results and positive findings in the literature, we purchased PhIP from three suppliers and found no detectable estrogenic activity in any batch. (1)H NMR spectroscopy confirmed the chemical identity of the tested stock solutions. Correct assay performance was confirmed by including positive and vehicle controls on every assay plate, and by demonstrating the expected responses to a panel of known estrogens (estradiol, bisphenol A, and genistein). Our results differ from those in the literature and, whilst the exact reason for this is unknown, we discuss possible explanations of the disparity. Our results provide no in vitro evidence for the classification of PhIP as an estrogen.
Authors:
Richard M Evans; Sinikka Rahte; Andreas Kortenkamp
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-12-29
Journal Detail:
Title:  Toxicology in vitro : an international journal published in association with BIBRA     Volume:  24     ISSN:  1879-3177     ISO Abbreviation:  Toxicol In Vitro     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-31     Completed Date:  2010-12-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8712158     Medline TA:  Toxicol In Vitro     Country:  England    
Other Details:
Languages:  eng     Pagination:  1757-63     Citation Subset:  IM    
Copyright Information:
Copyright 2010. Published by Elsevier Ltd.
Affiliation:
The School of Pharmacy, University of London, Centre for Toxicology, London, UK.
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MeSH Terms
Descriptor/Qualifier:
Cell Line, Tumor
Cell Proliferation / drug effects
Cooking
Dose-Response Relationship, Drug
Estrogens, Non-Steroidal / chemistry,  classification,  toxicity*
Genes, Reporter
Humans
Imidazoles / chemistry,  classification,  toxicity*
Magnetic Resonance Spectroscopy
Mutagens / chemistry,  classification,  toxicity*
Receptors, Estrogen / antagonists & inhibitors,  genetics,  metabolism
Reproducibility of Results
Chemical
Reg. No./Substance:
0/Estrogens, Non-Steroidal; 0/Imidazoles; 0/Mutagens; 0/Receptors, Estrogen; 105650-23-5/2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine

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


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