Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1983-11-23
pubmed:abstractText
Biochemical studies were undertaken with the human breast carcinoma cell line, 47-DN, to explore the mechanisms underlying cytotoxic synergy between tamoxifen (TAM) and the fluoropyrimidines, 5-fluorouracil (FUra) and 5-fluorouridine (FUrd). The influence of TAM pretreatment was measured on intracellular FUra accumulation, FUra nucleotide formation, and incorporation of fluoropyrimidines into cellular RNA. Unlike other modulators of FUra metabolism and toxicity. TAM decreased intracellular FUra accumulation and total RNA incorporation by 20 to 60%. Cells treated with TAM contained 10 to 20% less cellular RNA and showed reduced transcription and altered RNA turnover, independent of fluoropyrimidine treatment. Newly synthesized RNA from control and TAM-treated cells was fractionated by sucrose gradient centrifugation. The specific incorporation of FUrd (2 hr) was compared to that of FUra (6 hr) and labeled uridine incorporation into controls. Compared to its effect on uridine incorporation, TAM produced nearly twice as much FUra incorporation and 3 times as much FUra incorporation into 32 to 45S RNA. Since accumulation of this high-molecular-weight RNA has been associated with fluoropyrimidine toxicity and impaired ribosomal RNA processing, it is believed that TAM enriched the RNA-mediated toxicity of FUra and FUrd in this breast carcinoma cell line.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:volume
43
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5304-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1983
pubmed:articleTitle
Tamoxifen and 5-fluorouracil in breast cancer: modulation of cellular RNA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't