Linked Life Data

8339275

Source:http://linkedlifedata.com/resource/pubmed/id/8339275

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
1993-9-2
pubmed:abstractText
HCT-8 cells become rapidly resistant to either 4-h (HCT-8/4hR) or 7-day (HCT-8/7dR) repeated exposures to fluorouracil (FUra). The HCT-8/7dR cells were studied in more detail to determine their mechanism of resistance to FUra. Thymidylate synthase activity, binding of 5-fluorodeoxyuridylate to thymidylate synthase, and incorporation of FUra into RNA were not different between the parental and resistant sublines. However, folylpolyglutamate synthetase activity was markedly decreased in this subline using tetrahydrofolate, 5,10-methylenetetrahydrofolate, and methotrexate as substrates. Northern blot analysis revealed decreased folylpolyglutamate synthetase mRNA expression in HCT-8/7dR cells as compared to HCT-8 cells. These findings indicate that low-dose continuous exposure schedules to FUra are cytotoxic primarily due to inhibition of thymidylate synthase and underscores the role of 5,10-methylenetetrahydrofolate polyglutamates in this inhibition.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3677-80
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Decreased folylpolyglutamate synthetase expression: a novel mechanism of fluorouracil resistance.
pubmed:affiliation
Program of Molecular Pharmacology and Therapeutics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.