Linked Life Data

2814893

Source:http://linkedlifedata.com/resource/pubmed/id/2814893

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1989-12-18
pubmed:abstractText
A murine embryo culture model was developed to study the potential contribution of enzymatic bioactivation to the teratogenicity of phenytoin. To assess the relative embryonic and maternal contributions to bioactivation, embryos were cultured respectively alone or in the presence of an exogenous source of cytochromes P-450 (P-450), which are thought to bioactivate phenytoin to a teratogenic reactive intermediate. Embryological development from gestational day 9 to day 10 was assessed, and bioactivation was quantified by the irreversible binding of radiolabeled phenytoin to embryonic protein. Embryos cultured with phenytoin and an exogenous P-450 bioactivating system showed a significant decrease in the incidence of turning and closure of the anterior neuropore, yolk sac diameter, and protein content as well as growth retardation. In the absence of an exogenous P-450 system, phenytoin did not decrease the incidence of turning or anterior neuropore closure but did cause growth retardation and a lesser but significant reduction in yolk sac diameter and embryonic protein content. An exogenous P-450 system enhanced the bioactivation of phenytoin, although significant activity also was detectable in embryos cultured without an exogenous bioactivating system. These results suggest that the embryo itself can enzymatically bioactivate embryotoxically significant amounts of phenytoin, and that bioactivation and embryotoxicity can be further enhanced, qualitatively and quantitatively, by an exogenous P-450 system, implicating a possible maternal contribution to phenytoin teratogenicity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0040-3709
pubmed:author
pubmed:issnType
Print
pubmed:volume
40
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
311-20
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
Phenytoin embryotoxicity: role of enzymatic bioactivation in a murine embryo culture model.
pubmed:affiliation
Faculty of Pharmacy, University of Toronto, Ontario, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't