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Correlation between 5-fluorouracil metabolism and treatment response in two variants of C26 murine colon carcinoma
Following an i.p. dose of 150 mg kg(−1) 5-fluorouracil (5-FU), drug uptake and metabolism over a 2-h period were studied by in vivo (19)F magnetic resonance spectroscopy (MRS) for the murine colon carcinoma lines C26-B (5-FU-insensitive; n=11) and C26-10 (5-FU-sensitive; n=15) implanted s.c. in Balb...
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
2003
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2376920/ https://www.ncbi.nlm.nih.gov/pubmed/12915890 http://dx.doi.org/10.1038/sj.bjc.6601162 |
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author | Kamm, Y J L Peters, G J Hull, W E Punt, C J A Heerschap, A |
author_facet | Kamm, Y J L Peters, G J Hull, W E Punt, C J A Heerschap, A |
author_sort | Kamm, Y J L |
collection | PubMed |
description | Following an i.p. dose of 150 mg kg(−1) 5-fluorouracil (5-FU), drug uptake and metabolism over a 2-h period were studied by in vivo (19)F magnetic resonance spectroscopy (MRS) for the murine colon carcinoma lines C26-B (5-FU-insensitive; n=11) and C26-10 (5-FU-sensitive; n=15) implanted s.c. in Balb/C mice. Time courses for tumour growth, intracellular levels of FdUMP, thymidylate synthase (TS) activity, and 5-FU in RNA were also determined, and the effects of a 9.5-min period of carbogen breathing, starting 1 min before drug administration, on MRS-detected 5-FU metabolism and tumour growth curves were examined. Both tumour variants generated MRS-detectable 5-FU nucleotides and showed similar initial growth inhibition after treatment. However, the growth rate of C26-B tumours returned to normal, while the sensitive C26-10 tumours, which produced larger fluoronucleotide pools, still showed moderate growth inhibition. Carbogen breathing did not significantly influence 5-FU uptake or fluoronucleotide production but did significantly enhance growth inhibition in C26-10 tumours. While both tumour variants exhibited incorporation of 5-FU into RNA and inhibition of TS via FdUMP, clearance of 5-FU from RNA and recovery of TS activity were greater for the insensitive C26-B line, indicating that these processes, in addition to 5-FU uptake and metabolism, may be important determinants of drug sensitivity and treatment response. |
format | Text |
id | pubmed-2376920 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2003 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-23769202009-09-10 Correlation between 5-fluorouracil metabolism and treatment response in two variants of C26 murine colon carcinoma Kamm, Y J L Peters, G J Hull, W E Punt, C J A Heerschap, A Br J Cancer Experimental Therapeutics Following an i.p. dose of 150 mg kg(−1) 5-fluorouracil (5-FU), drug uptake and metabolism over a 2-h period were studied by in vivo (19)F magnetic resonance spectroscopy (MRS) for the murine colon carcinoma lines C26-B (5-FU-insensitive; n=11) and C26-10 (5-FU-sensitive; n=15) implanted s.c. in Balb/C mice. Time courses for tumour growth, intracellular levels of FdUMP, thymidylate synthase (TS) activity, and 5-FU in RNA were also determined, and the effects of a 9.5-min period of carbogen breathing, starting 1 min before drug administration, on MRS-detected 5-FU metabolism and tumour growth curves were examined. Both tumour variants generated MRS-detectable 5-FU nucleotides and showed similar initial growth inhibition after treatment. However, the growth rate of C26-B tumours returned to normal, while the sensitive C26-10 tumours, which produced larger fluoronucleotide pools, still showed moderate growth inhibition. Carbogen breathing did not significantly influence 5-FU uptake or fluoronucleotide production but did significantly enhance growth inhibition in C26-10 tumours. While both tumour variants exhibited incorporation of 5-FU into RNA and inhibition of TS via FdUMP, clearance of 5-FU from RNA and recovery of TS activity were greater for the insensitive C26-B line, indicating that these processes, in addition to 5-FU uptake and metabolism, may be important determinants of drug sensitivity and treatment response. Nature Publishing Group 2003-08-18 2003-08-12 /pmc/articles/PMC2376920/ /pubmed/12915890 http://dx.doi.org/10.1038/sj.bjc.6601162 Text en Copyright © 2003 Cancer Research UK 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 | Experimental Therapeutics Kamm, Y J L Peters, G J Hull, W E Punt, C J A Heerschap, A Correlation between 5-fluorouracil metabolism and treatment response in two variants of C26 murine colon carcinoma |
title | Correlation between 5-fluorouracil metabolism and treatment response in two variants of C26 murine colon carcinoma |
title_full | Correlation between 5-fluorouracil metabolism and treatment response in two variants of C26 murine colon carcinoma |
title_fullStr | Correlation between 5-fluorouracil metabolism and treatment response in two variants of C26 murine colon carcinoma |
title_full_unstemmed | Correlation between 5-fluorouracil metabolism and treatment response in two variants of C26 murine colon carcinoma |
title_short | Correlation between 5-fluorouracil metabolism and treatment response in two variants of C26 murine colon carcinoma |
title_sort | correlation between 5-fluorouracil metabolism and treatment response in two variants of c26 murine colon carcinoma |
topic | Experimental Therapeutics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2376920/ https://www.ncbi.nlm.nih.gov/pubmed/12915890 http://dx.doi.org/10.1038/sj.bjc.6601162 |
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