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Studies Concerned with Overcoming Resistance to Methotrexate: A Comparison of the Effects of Methotrexate and 2,4-Diamino-5-(3′,4′-Dichlorophenyl)-6-Methylpyrimidine (BW50197) on the Colony Forming Ability of L5178Y Cells

The effects of methotrexate (MTX) and 2,4-diamino-5-(3′,4′-dichlorophenyl)-6-methylpyrimidine (BW50197) on the colony forming ability of L5178Y cells were compared. Two sub-lines of cells were used, one sensitive to methotrexate and the other resistant. In addition, the inhibitory effects of BW50197...

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Autores principales: Hill, Bridget T., Goldie, J. H., Price, L. A.
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 1973
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2008983/
https://www.ncbi.nlm.nih.gov/pubmed/4743908
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author Hill, Bridget T.
Goldie, J. H.
Price, L. A.
author_facet Hill, Bridget T.
Goldie, J. H.
Price, L. A.
author_sort Hill, Bridget T.
collection PubMed
description The effects of methotrexate (MTX) and 2,4-diamino-5-(3′,4′-dichlorophenyl)-6-methylpyrimidine (BW50197) on the colony forming ability of L5178Y cells were compared. Two sub-lines of cells were used, one sensitive to methotrexate and the other resistant. In addition, the inhibitory effects of BW50197 against dihydrofolate reductase (DHFR) extracted from the MTX resistant cells were compared with those of MTX and pyrimethamine. It was found that although BW50197 was a less effective inhibitor of DHFR than MTX, it was superior to MTX at high concentrations in killing MTX resistant cells, and this superiority increased with the time of exposure to the drugs. These findings suggest that (a) when antifolate compounds are screened for antitumour activity it is insufficient simply to assess them on the basis of their ability to inhibit DHFR and (b) BW50197 should be given clinically so as to achieve the highest possible tissue concentration for the longest possible time consistent with the safety of the patient.
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spelling pubmed-20089832009-09-10 Studies Concerned with Overcoming Resistance to Methotrexate: A Comparison of the Effects of Methotrexate and 2,4-Diamino-5-(3′,4′-Dichlorophenyl)-6-Methylpyrimidine (BW50197) on the Colony Forming Ability of L5178Y Cells Hill, Bridget T. Goldie, J. H. Price, L. A. Br J Cancer Articles The effects of methotrexate (MTX) and 2,4-diamino-5-(3′,4′-dichlorophenyl)-6-methylpyrimidine (BW50197) on the colony forming ability of L5178Y cells were compared. Two sub-lines of cells were used, one sensitive to methotrexate and the other resistant. In addition, the inhibitory effects of BW50197 against dihydrofolate reductase (DHFR) extracted from the MTX resistant cells were compared with those of MTX and pyrimethamine. It was found that although BW50197 was a less effective inhibitor of DHFR than MTX, it was superior to MTX at high concentrations in killing MTX resistant cells, and this superiority increased with the time of exposure to the drugs. These findings suggest that (a) when antifolate compounds are screened for antitumour activity it is insufficient simply to assess them on the basis of their ability to inhibit DHFR and (b) BW50197 should be given clinically so as to achieve the highest possible tissue concentration for the longest possible time consistent with the safety of the patient. Nature Publishing Group 1973-09 /pmc/articles/PMC2008983/ /pubmed/4743908 Text en https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Articles
Hill, Bridget T.
Goldie, J. H.
Price, L. A.
Studies Concerned with Overcoming Resistance to Methotrexate: A Comparison of the Effects of Methotrexate and 2,4-Diamino-5-(3′,4′-Dichlorophenyl)-6-Methylpyrimidine (BW50197) on the Colony Forming Ability of L5178Y Cells
title Studies Concerned with Overcoming Resistance to Methotrexate: A Comparison of the Effects of Methotrexate and 2,4-Diamino-5-(3′,4′-Dichlorophenyl)-6-Methylpyrimidine (BW50197) on the Colony Forming Ability of L5178Y Cells
title_full Studies Concerned with Overcoming Resistance to Methotrexate: A Comparison of the Effects of Methotrexate and 2,4-Diamino-5-(3′,4′-Dichlorophenyl)-6-Methylpyrimidine (BW50197) on the Colony Forming Ability of L5178Y Cells
title_fullStr Studies Concerned with Overcoming Resistance to Methotrexate: A Comparison of the Effects of Methotrexate and 2,4-Diamino-5-(3′,4′-Dichlorophenyl)-6-Methylpyrimidine (BW50197) on the Colony Forming Ability of L5178Y Cells
title_full_unstemmed Studies Concerned with Overcoming Resistance to Methotrexate: A Comparison of the Effects of Methotrexate and 2,4-Diamino-5-(3′,4′-Dichlorophenyl)-6-Methylpyrimidine (BW50197) on the Colony Forming Ability of L5178Y Cells
title_short Studies Concerned with Overcoming Resistance to Methotrexate: A Comparison of the Effects of Methotrexate and 2,4-Diamino-5-(3′,4′-Dichlorophenyl)-6-Methylpyrimidine (BW50197) on the Colony Forming Ability of L5178Y Cells
title_sort studies concerned with overcoming resistance to methotrexate: a comparison of the effects of methotrexate and 2,4-diamino-5-(3′,4′-dichlorophenyl)-6-methylpyrimidine (bw50197) on the colony forming ability of l5178y cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2008983/
https://www.ncbi.nlm.nih.gov/pubmed/4743908
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