Document Detail

The use of a fluorescent methotrexate probe to monitor the effects of three vinca alkaloids on a mixed population of parental L1210 and gene-amplified methotrexate-resistant cells by flow cytometry.
MedLine Citation:
PMID:  6733843     Owner:  NLM     Status:  MEDLINE    
Cells resistant to methotrexate (L1210/R7A) and possessing an increased level of dihydrofolate reductase due to gene amplification can be detected by the technique of flow cytofluorimetry using a new fluorescent derivative of methotrexate (F-MTX) based on a putrescine linker. Comparative studies of dihydrofolate reductase enzyme and cell growth inhibition following treatment with methotrexate and F-MTX suggest that the two agents possess similar modes of action. In an artificially mixed population of cells sensitive and resistant to methotrexate it is possible, using F-MTX, to recognise and separate distinct cell subpopulations showing differential fluorescence using a fluorescence-activated cell sorter (FACS IV). The selective removal of the resistant cells within a mixed population of sensitive and resistant cells has been demonstrated for 5 X 10(-8) M vinblastine by means of flow cytometry. The effectiveness of the vinca alkaloids decreases in the order vinblastine greater than vindesine greater than vincristine, which previously was shown to be the order of effectiveness in producing collateral sensitivity.
D G Poppitt; A T McGown; B W Fox
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer chemotherapy and pharmacology     Volume:  13     ISSN:  0344-5704     ISO Abbreviation:  Cancer Chemother. Pharmacol.     Publication Date:  1984  
Date Detail:
Created Date:  1984-08-08     Completed Date:  1984-08-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7806519     Medline TA:  Cancer Chemother Pharmacol     Country:  GERMANY, WEST    
Other Details:
Languages:  eng     Pagination:  54-7     Citation Subset:  IM    
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MeSH Terms
Cell Division / drug effects
Cell Line
Cell Survival / drug effects
Drug Resistance
Flow Cytometry / methods
Fluorescent Dyes / diagnostic use*
Gene Amplification / drug effects
Leukemia L1210 / genetics,  metabolism*
Methotrexate / analogs & derivatives*,  diagnostic use,  metabolism*
Tetrahydrofolate Dehydrogenase / genetics,  metabolism*
Vinca Alkaloids / pharmacology*
Reg. No./Substance:
0/Fluorescent Dyes; 0/Vinca Alkaloids; 0/fluoresceinated methotrexate; 59-05-2/Methotrexate; EC Dehydrogenase

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

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