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Penetration and binding of vinblastine and 5-fluorouracil in cellular spheroids

  • Original Articles
  • Drug Studies, 5-Fluorouracil, Spheroids, Vinblastine
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Summary

The kinetics of the penetration and binding of the two commonly used antitumour drugs vinblastine and 5-fluorouracil in nonvascularized tumour tissue were studied. Multicellular human tumour spheroids (glioma U-118 MG and thyroid cancer HTh-7) were used as a model system. Radiolabelled drugs were used in all studies. To avoid disturbances in the distribution of unbound drugs a dry histological technique was used in combination with contact autoradiography. In addition, quantitative measurements of the accumulation and binding of the drugs were made. The results showed that vinblastine penetrated the spheroids less efficiently than 5-fluorouracil. Vinblastine required about 2 h to be isotropically distributed within the studied spheroids, while only a few minutes were required for 5-fluorouracil. Vinblastine seemed to be accumulated in the peripheral parts of the spheroids within 15 min. High concentrations of 5-fluorouracil, isotropically distributed in the spheroids, were observed after 2 h of incubation. Significant amounts (about half) of the accumulated drugs resisted gentle washing for 3x20 s plus 15 min in fresh medium. The limited penetration of vinblastine correlated well with a previously observed high resistance of spheroids to treatments of short duration with this drug.

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Authors and Affiliations

  1. Department of Physical Biology, The Gustaf Werner Institute, Box 531, S-751 21, Uppsala, Sweden

    Thore Nederman

  2. The Max Planck Institute for Systemphysiology, Rheinlanddamm 201, D-4600, Dortmund 1, Federal Republic of Germany

    Thore Nederman

  3. Department of Radiobiology, The National Defence Research Institute, FOA-4, S-901 82, Umeå, Sweden

    Jörgen Carlsson

Authors
  1. Thore Nederman
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  2. Jörgen Carlsson
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Nederman, T., Carlsson, J. Penetration and binding of vinblastine and 5-fluorouracil in cellular spheroids. Cancer Chemother. Pharmacol. 13, 131–135 (1984). https://doi.org/10.1007/BF00257130

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  • DOI: https://doi.org/10.1007/BF00257130

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