Linked Life Data

2171601

Source:http://linkedlifedata.com/resource/pubmed/id/2171601

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1990-12-26
pubmed:abstractText
The nucleoside transport inhibitor dipyridamole can potentiate the cytotoxicity of methotrexate by a mechanism that was thought to be related to the inhibition of thymidine salvage. In human ovarian carcinoma cells thymidine only partly reversed the in vitro cytotoxicity of methotrexate plus dipyridamole at sub-millimolar concentrations, above which the cytotoxicity of thymidine itself became evident. Hypoxathine with thymidine, or hypoxanthine alone at a higher concentration, completely reversed methotrexate and methotrexate plus dipyridamole cytotoxicity. The effects of dipyridamole on cellular cyclic adenosine monophosphate (cAMP) levels and on 3H-methotrexate efflux in 2008 cells were examined. At 10 mumol/l, dipyridamole did not alter cAMP content or methotrexate influx in ovarian carcinoma cells, but reduced the rate of efflux of 3H-methotrexate by 25%. In Chinese hamster ovary cells and their folylpolyglutamyl synthase-deficient variant AUX B1, the reduced methotrexate efflux by dipyridamole was not due to increased polyglutamation, since increased retention was observed in both cell lines. The data support the hypothesis that dipyridamole potentiated the activity of methotrexate by inhibiting the salvage of hypoxanthine, and to a lesser extent, that of thymidine. The ability of dipyridamole to increase the cellular retention of methotrexate was probably a non-specific action of dipyridamole on the cell membrane, and may have a role in the observed synergy.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0959-8049
pubmed:author
pubmed:issnType
Print
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
907-11
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1990
pubmed:articleTitle
Role of hypoxanthine and thymidine in determining methotrexate plus dipyridamole cytotoxicity.
pubmed:affiliation
Department of Physiology and Pharmacology, School of Veterinary Medicine, Purdue University, West Lafayette, Indiana 47907.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't