Document Detail


The concentration of 5-phosphoribosyl 1-pyrophosphate in monolayer tumor cells and the effect of various pyrimidine antimetabolites.
MedLine Citation:
PMID:  2581824     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
5-Phosphoribosyl 1-pyrophosphate (PRPP) was determined in several murine and human cancer cell lines grown in monolayer, and harvested by trypsinization. For all cell lines a large variation in the PRPP concentration (5-1300 pmol/ 10(6) cells was found. A 1-hr incubation in Dullbecco's medium reduced the variation in PRPP concentration. After this incubation the highest concentration was found in the murine B16 melanoma cell line (about 200 pmol/10(6) cells). The human melanoma cell lines IGR3 and M5 and the human colon carcinoma cell line WiDr contained about 100 pmol/10(6) cells. After this preincubation of 1-hr these cell suspensions were used to study the effect of several antimetabolites on PRPP concentration. A 2-hr incubation with 1mM N-(phosphonacetyl)-L-aspartate (PALA) increased the PRPP concentration only in M5 cells, whereas methotrexate caused an increase in all cell lines. When 5-fluorouracil (5FU) was added, no significant decrease was found in any cell line. Addition of 5FU after a 2-hr preincubation with PALA resulted in a lower concentration in B16, M5 and WiDr cells. The prodrug, 5-fluoro-5' deoxyuridine altered the PRPP concentration only in in WiDr cells when it was added after PALA. The activity of the 5FU metabolizing enzyme orotate phosphoribosyl transferase was comparable in B16, M5 and WiDr cells, but much lower in IGR3 cells.
Authors:
G J Peters; E Laurensse; A Leyva; H M Pinedo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The International journal of biochemistry     Volume:  17     ISSN:  0020-711X     ISO Abbreviation:  Int. J. Biochem.     Publication Date:  1985  
Date Detail:
Created Date:  1985-06-26     Completed Date:  1985-06-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0250365     Medline TA:  Int J Biochem     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  95-9     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Aspartic Acid / analogs & derivatives,  pharmacology
Cell Line
Cells, Cultured
Fluorouracil / pharmacology
Humans
Methotrexate / pharmacology
Neoplasms / metabolism*
Ornithine Decarboxylase / metabolism
Orotate Phosphoribosyltransferase / metabolism
Pentosephosphates / metabolism*
Phosphonoacetic Acid / analogs & derivatives,  pharmacology
Phosphoribosyl Pyrophosphate / metabolism*
Chemical
Reg. No./Substance:
0/Pentosephosphates; 4408-78-0/Phosphonoacetic Acid; 51-21-8/Fluorouracil; 51321-79-0/NSC 224131; 56-84-8/Aspartic Acid; 59-05-2/Methotrexate; 7540-64-9/Phosphoribosyl Pyrophosphate; EC 2.4.2.10/Orotate Phosphoribosyltransferase; EC 4.1.1.17/Ornithine Decarboxylase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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