Linked Life Data

9339481

Source:http://linkedlifedata.com/resource/pubmed/id/9339481

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1 Pt 1
pubmed:dateCreated
1997-11-14
pubmed:abstractText
One of the components of our research program is development of a mode-of-action screening battery to detect several different types of endocrine-active compounds (EACs). Our working hypothesis is that a comprehensive short-term in vivo/in vitro battery can be developed to identify endocrine toxicants using a collection of endpoints. The goals of this battery are that it be quick, cost effective, and predictive. The purpose of this battery is to identify potential EACs and to assess their potency in order to prioritize compounds for further study. Two in vivo screens (intact male and ovariectomized female rats) are being evaluated for their ability to detect several different types of endocrine activity. To validate this screen, 15 compounds with known endocrine activities are being used to evaluate a collection of different endpoints for their variability, stability over time, predictiveness, and dose dependency. These positive controls were chosen because they can modulate development, reproduction, or cancer. The advantage of an in vivo screen is that it utilizes a metabolically and physiologically intact system. The male in vivo battery will be used to assess several different types of endocrine activity, primarily by using a comprehensive hormonal battery. The female in vivo battery will be used to identify compounds which are either estrogenic/antiestrogenic or can alter the prolactin pathway. The in vitro portion of the screening battery consists of a yeast transactivation system (YTS). The YTS is being evaluated for its ability to identify compounds which are agonists or antagonists to the estrogen, androgen, or progesterone receptors. The expression of mammalian receptors in yeast allows for assessment of steroid-dependent transcriptional activators. The value of this system is that it can be used as a routine screen for compounds that interact with steroid receptors. Alterations in ligand binding to these receptors can be correlated with alterations in development via masculinization of females and/or feminization of males, decreases in reproductive success, or modulation of cancer incidence from in vivo tests. The in vivo and in vitro screens are designed to be run in parallel with built-in redundancy in order to reduce the probability of false-negative/ positive responses.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0273-2300
pubmed:author
pubmed:issnType
Print
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
60-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Development of a Tier I screening battery for detecting endocrine-active compounds (EACs).
pubmed:affiliation
DuPont-Haskell Laboratory for Toxicology and Industrial Medicine, Newark, Delaware 19714, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't