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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1982-9-10
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pubmed:abstractText |
We have previously demonstrated a highly significant relationship (P less than 0.0001) between the incorporation of 5-fluorouracil (5-FU) into total cellular RNA and loss of clonogenic survival of the human MCF-7 breast carcinoma cell line. The present studies explore the applicability of this relationship to MCF-7 cells exposed to 5-FU and modulating agents such as PALA, MTX, and MMPR. PALA treatment produces a minimal increase in the absolute amount of 5-FU incorporated into total cellular RNA, but it results in a three-fold enhancement of the [3H]FU/32P ratio, which measures 5-FU misincorporation into newly synthesized RNA. MTX and MMPR increase intracellular PRPP levels up to four-fold; nevertheless these agents result in only minimal increases in absolute (5-FU)RNA formation. In contrast, the relative incorporation of 5-FU into newly synthesized RNA of MTX- or MMPR-treated cells is increased 2.5-fold. The combination of PALA/MMPR results in a two-fold absolute increase in (5-FU)RNA formation and a nine-fold enhancement of the [3H]FU/32P ratio. Combinations of modulating agents with 5-FU result in more than additive decreases in MCF-7 clonogenic survival. The relationship between 5-FU incorporation into RNA and loss of clonogenic survival was highly significant (P less than 0.0002) when corrected for newly synthesized RNA, while the correlation with absolute amounts of (5-FU)RNA formation was less significant (P less than 0.05). These studies demonstrate that the relationship previously established between (5-FU)RNA formation and loss of clonogenic survival should be corrected for the amount of newly synthesized RNA when 5-FU is combined with modulating agents that alter rates of RNA synthesis.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:issn |
0344-5704
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
8
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
87-91
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:7094201-Breast Neoplasms,
pubmed-meshheading:7094201-Cells, Cultured,
pubmed-meshheading:7094201-Female,
pubmed-meshheading:7094201-Fluorouracil,
pubmed-meshheading:7094201-Humans,
pubmed-meshheading:7094201-Methotrexate,
pubmed-meshheading:7094201-Methylthioinosine,
pubmed-meshheading:7094201-RNA, Neoplasm
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pubmed:year |
1982
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pubmed:articleTitle |
Modulation of 5-FU metabolism in human MCF-7 breast carcinoma cells.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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