Linked Life Data

2528057

Source:http://linkedlifedata.com/resource/pubmed/id/2528057

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1989-9-29
pubmed:abstractText
Mouse FM3A mammary adenocarcinoma cells exposed to the specific thymidylate synthetase (TS) inhibitor 10-propargyl-5,8-dideazafolate (PDF) responded by overproducing TS up to 200-fold. In the absence of inhibitor, the elevation of TS levels decayed with a half-life of about 4 weeks. Southern blot analysis of restricted DNA from the PDF-resistant cells using a TS-specific probe showed that the TS gene was amplified to the same extent as enzyme levels. The PDF-resistant cells showed moderate cross-resistance to growth inhibition by 5-fluoro-2'-deoxyuridine, which increased with TS overproduction, but cross-resistance to 5-fluorouracil (FUra) was less (2- to 3-fold) and did not change with increased TS levels. TS activity, measured as release of tritium from [5-3H]2'-deoxyuridine, was no higher in the intact PDF-resistant cells than in wild-type cells. Inhibition of TS activity by FUra in the wild-type cells was accompanied by a proportional decrease in the amount of free TS, presumably due to formation of the tight binding complex of TS with 5-fluoro-2'-deoxyuridylate and 5,10'-methylenetetrahydrofolate. However, in the PDF-resistant cells, most the TS was still in the free form even though TS activity was substantially (85-90%) inhibited. Addition of folinic acid did not change either the sensitivity of the cells to FUra or the rates of tritium release in the cells having overproduced TS. These results are consistent with compartmentalization of TS, possibly in a multienzyme complex.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
36
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
219-23
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
Activity of thymidylate synthetase and its inhibition by 5-fluorouracil in highly enzyme-overproducing cells resistant to 10-propargyl-5,8-dideazafolate.
pubmed:affiliation
Department of Biochemistry, University of Southern California School of Medicine, Los Angeles 90033.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't