Linked Life Data

7245091

Source:http://linkedlifedata.com/resource/pubmed/id/7245091

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1981-8-20
pubmed:abstractText
Preimplantation mouse embryos were cultured for 48 hours from the four-cell and eight-cell stage to the blastocyst stage in the presence of cyclophosphamide (CPA) or one of its metabolites-4-hydroperoxy-CPA (4-HP-CPA), phosphoramide mustard (PAM), and acrolein (Acr)--to identify the metabolite which is embryotoxic after CPA treatment of pregnant mice during the preimplantation period. The dose-response relations for the inhibition of blastulation revealed identical inhibition curves for PAM and 4-HP-CPA (in solution 4-HP-CPA immediately decomposes to 4-hydroxy-CPA (4-OH-CPA)). These two metabolites are inhibiting blastulation in vitro at concentrations that are 10,000 times lower than CPA and 100 times lower than acrolein. When blastocysts which had developed in the presence of CPA and its metabolites in vitro were subsequently cultured in inhibitor-free medium NCTC-109, the same dose-response relationship pattern was obtained. Since 4-OH-CPA decomposes into acrolein and PAM in vivo and in vitro and since PAM and 4-OH-CPA exhibit identical embryotoxicity towards preimplantation embryos in vitro, PAM probably also is an active embryotoxic CPA metabolite in vivo before implantation. This result is discussed in relation to the importance of alkylating CPA metabolites in cancer treatment and in teratological studies during organogenesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0040-3709
pubmed:author
pubmed:issnType
Print
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7-13
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1981
pubmed:articleTitle
Investigation on cyclophosphamide treatment during the preimplantation period. II. In vitro studies on the effects of cyclophosphamide and its metabolites 4-OH-cyclophosphamide, phosphoramide mustard, and acrolein on blastulation of four-cell and eight-cell mouse embryos and on their subsequent development during implantation.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't