Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1994-6-2
pubmed:abstractText
The cellular pharmacology of the tritium-labeled cisplatin analogue dichloro(ethylenediamine)platinum(II) ([3H]DEP) was compared in cisplatin-sensitive 2008 and resistant 2008/C13*5.25 human ovarian carcinoma cells. The cellular content of total [3H], ultrafiltrable [3H], and free native [3H]DEP was measured during and following incubation with 5 microM [3H]DEP. While the rate constant for [3H]DEP uptake in the resistant cells was reduced to 25% of that in the sensitive cells, DNA intrastrand adduct formation was reduced even further to 11%, indicating the presence of defects in both uptake and the ability of intracellular drug to access or react with DNA. The latter could not be accounted for by enhanced repair. Together, these defects were sufficient to account for the 11-fold level of resistance. At steady state, the intracellular to extracellular concentration ratio for native [3H]DEP was 7.7 in the sensitive cells and 11.7 in the resistant cells, suggesting the presence of a trapping or concentrative mechanism. Thus, despite the slower initial influx, the resistant cells eventually accumulated more free [3H]DEP than the sensitive cells. We conclude that the resistant phenotype in these cells is accounted for primarily by impaired uptake and decreased reaction of [3H]DEP with DNA rather than by changes in efflux or DNA repair.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
54
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2680-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Cellular pharmacology of dichloro(ethylenediamine)platinum(II) in cisplatin-sensitive and resistant human ovarian carcinoma cells.
pubmed:affiliation
Department of Medicine, University of California, San Diego, La Jolla 92093-0812.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't