Issues of Normal Tissue Toxicity in Patient and Animal Studies - Effect of Carbogen Breathing in Rats after 5-Fluorouracil Treatment

Authors

  • John R. Griffiths From the CRC Biomedical Magnetic Resonance Research Group, Department of Biochemistry and Immunology, St. George‘s Hospital Medical School, London, UK
  • Dominick J.O. McIntyre From the CRC Biomedical Magnetic Resonance Research Group, Department of Biochemistry and Immunology, St. George‘s Hospital Medical School, London, UK
  • Franklyn A. Howe From the CRC Biomedical Magnetic Resonance Research Group, Department of Biochemistry and Immunology, St. George‘s Hospital Medical School, London, UK
  • Paul M.J. McSheehy From the CRC Biomedical Magnetic Resonance Research Group, Department of Biochemistry and Immunology, St. George‘s Hospital Medical School, London, UK
  • Agatha S.E. Ojugo From the CRC Biomedical Magnetic Resonance Research Group, Department of Biochemistry and Immunology, St. George‘s Hospital Medical School, London, UK
  • Loreta M. Rodrigues From the CRC Biomedical Magnetic Resonance Research Group, Department of Biochemistry and Immunology, St. George‘s Hospital Medical School, London, UK
  • Peter Wadsworth Safety of Medicines Department, AstraZeneca, Macclesfield, Cheshire, UK
  • Natasha M. Price From the CRC Biomedical Magnetic Resonance Research Group, Department of Biochemistry and Immunology, St. George‘s Hospital Medical School, London, UK
  • Fiona Lofts Departments of Medical Oncology, St. George‘s Hospital Medical School, London, UK
  • Grainne Nicholson Departments of Anaesthetics, St. George‘s Hospital Medical School, London, UK
  • Kees Smid Department of Medical Oncology, University Hospital VU, Amsterdam, The Netherlands
  • Paul Noordhuis Department of Medical Oncology, University Hospital VU, Amsterdam, The Netherlands
  • Godefridus J. Peters Department of Medical Oncology, University Hospital VU, Amsterdam, The Netherlands
  • Marion Stubbs From the CRC Biomedical Magnetic Resonance Research Group, Department of Biochemistry and Immunology, St. George‘s Hospital Medical School, London, UK

DOI:

https://doi.org/10.1080/028418601750444150

Abstract

Non-invasive magnetic resonance spectroscopy (MRS) can be used in the clinic to monitor the pharmacokinetics of the chemotherapeutic drug 5-fluorouracil (5-FU) and the effects of modifiers. We report two studies of 5-FU toxicity in normal tissue?one with patients and the other an animal study. 1) 19F MRS signals from fluoronucleotides, cytotoxic anabolites of 5-FU metabolism, were observed in the livers of two patients treated with 5-FU for colorectal cancer, shown by computed tomography (CT) and ultrasound (US) to have no liver metastases. This is the first report of non-invasive monitoring of toxic 5-FU metabolites in normal human tissues. 2) In animals, carbogen breathing enhances tumour uptake and the efficacy of 5-FU, and the method is under trial in patients. This study demonstrates that there were no significant effects of carbogen breathing on the levels of 5-FU and its metabolites in normal rat tissues, or on the histology of the tissues assessed after treatment.

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Published

2001-01-01

How to Cite

Griffiths, J. R., McIntyre, D. J., Howe, F. A., McSheehy, P. M., Ojugo, A. S., Rodrigues, L. M., … Stubbs, M. (2001). Issues of Normal Tissue Toxicity in Patient and Animal Studies - Effect of Carbogen Breathing in Rats after 5-Fluorouracil Treatment. Acta Oncologica, 40(5), 609–614. https://doi.org/10.1080/028418601750444150

Issue

Vol. 40 No. 5 (2001): Acta Oncologica

Section

Articles