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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-4-15
pubmed:abstractText
The rat uterotrophic assay is a widely used screening test for the detection of estrogenic, endocrine-disrupting chemicals. Although much attention has been paid to identifying protocol variables and reproducibility between laboratories the question whether toxicodynamic and toxicokinetic variations of different strains may affect their sensitivity to estrogenic stimuli has been rarely addressed. We have compared the estrogenic activity of the environmental chemicals genistein (GEN), bisphenol A (BPA) and p- tert-octylphenol (OCT) in DA/Han (DA), Sprague-Dawley (SD) and Wistar (WIS) rats after repeated oral application. Rats were treated per os for 3 days with different doses of these weakly estrogenic compounds and the potent reference estrogen ethinylestradiol (EE). Then uterine wet weight, thickness of the uterine epithelium, uterine gene expression of clusterin (CLU), and thickness of the vaginal epithelium were examined as parameters for estrogenic potency of the test compounds in the three strains of rats. The uterotrophic response to treatment with BPA, OCT and GEN was similar in the three strains, and allowed us to rank them as GEN being more potent than OCT, and BPA being the weakest estrogen. This was confirmed by analysis of other biological endpoints, despite some differences in the magnitude of their response among strains and to distinct compounds. For instance, the uterus wet weight response to EE treatment indicated lower sensitivity of SD rats than that of DA and WIS rats, but this was not observed for responses of the uterine or vaginal epithelium. Moreover, blood concentrations were assessed at the time of killing and related to biological responses: plasma levels of total and unconjugated BPA and GEN depended upon the dose administered and varied to some extent within treatment groups and among the three rat strains. However, there was no good correlation in the three strains between individual compound concentrations analysed 24 h after the last dose and the uterotrophic wet weights. Summarising our results, we conclude that the sensitivity of various biological endpoints can differ slightly between strains of rats. On the other hand, our data demonstrate that the choice of the rat strain does not lead to pronounced differences in the evaluation of estrogenic activities of chemicals, especially when different biological endpoints are included in the analysis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0340-5761
pubmed:author
pubmed:issnType
Print
pubmed:volume
78
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
183-93
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:14689164-Administration, Oral, pubmed-meshheading:14689164-Animals, pubmed-meshheading:14689164-Clusterin, pubmed-meshheading:14689164-Dose-Response Relationship, Drug, pubmed-meshheading:14689164-Down-Regulation, pubmed-meshheading:14689164-Epithelium, pubmed-meshheading:14689164-Estrogens, pubmed-meshheading:14689164-Female, pubmed-meshheading:14689164-Gene Expression, pubmed-meshheading:14689164-Genistein, pubmed-meshheading:14689164-Glycoproteins, pubmed-meshheading:14689164-Molecular Chaperones, pubmed-meshheading:14689164-Organ Size, pubmed-meshheading:14689164-Phenols, pubmed-meshheading:14689164-RNA, Messenger, pubmed-meshheading:14689164-Rats, pubmed-meshheading:14689164-Rats, Sprague-Dawley, pubmed-meshheading:14689164-Rats, Wistar, pubmed-meshheading:14689164-Uterus, pubmed-meshheading:14689164-Vagina
pubmed:year
2004
pubmed:articleTitle
Comparative responses of three rat strains (DA/Han, Sprague-Dawley and Wistar) to treatment with environmental estrogens.
pubmed:affiliation
Institut für Morphologie und Tumorforschung, Deutsche Sporthochschule Köln, Cologne, Germany.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't