Linked Life Data

20551240

Source:http://linkedlifedata.com/resource/pubmed/id/20551240

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2010-8-19
pubmed:abstractText
Cryopreserved rat hepatocytes entrapped within an alginate matrix, commercially available as Liverbeads, were evaluated for their relevance as a screening tool for gene induction in vitro, using quantitative real-time reverse transcriptase-polymerase chain reaction. They were treated with the reference compounds beta-naphthoflavone (BNF), phenobarbital (PB), pregnenolone 16alpha-carbonitrile (PCN), and clofibric acid (CLO) and analyzed for mRNA levels of Cyp1a1, Cyp2b1, Cyp3a1, Cyp4a1, Ugt1a6, and Ugt2b1. In addition, for PB and PCN, the results were compared with those obtained in rat liver in vivo. For each inducer, the gene induction profiles obtained with the Liverbeads in vitro model were time- and dose-dependent. The in vitro gene expression profiles confirmed the corresponding known P450 and UGT induction by each reference compound. In particular, the most strongly induced genes were Cyp1a1 by BNF, Cyp2b1 by PB, Cyp3a1 and Ugt2b1 by PCN, and Cyp4a1 and Cyp2b1 by CLO. Other genes investigated were also induced by the reference compounds, but the expression levels were lower, and increases were seen only after prolonged treatment. In particular, Ugt1a6 and Cyp2b1 were increased by BNF, Cyp1a1, Cyp3a1, and Ugt2b1 by PB, and Cyp3a1 and Ugt2b1 by CLO. All of these results correlated well with published in vitro data and our in vivo data. In conclusion, our results suggest that Liverbeads is a relevant and useful in vitro screening tool for determining gene induction profiles of new molecules. In addition, because Liverbeads from different species are available, this tool offers the possibility to conduct interspecies comparisons.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1521-009X
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1598-604
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Liverbeads: a practical and relevant in vitro model for gene induction investigations.
pubmed:affiliation
Bayer Cropscience, Toxicologie Recherche, Sophia-Antipolis, France
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't