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Standardized kinetic microassay to quantify differential chemosensitivity on the basis of proliferative activity

  • Original Papers
  • Experimental Oncology
  • Published:
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Summary

Conventionally in vitro cytotoxicity assays are performed as single-end-point determinations. To compensate for the diversity of growth rates among different cell lines in this report we describe a computerized kinetic chemosensitivity assay based on quantification of biomass by staining cells with crystal violet. As a prerequisite four human breast cancer cell line (MDA-MB-231, MCF-7, T-47-D and ZR-75-1) were characterized with regard to oestrogen and progesterone receptor content, modal chromosome number and proliferation kinetics depending on the number of passages in culture. With prolonged time in culture for ZR-75-1 exposed to various concentrations of cisplatinum a dose-related increase in drug effect was observed. Owing to a correction of the T/C values for the initial cell mass (at the time when drug is added) a sharp distinction between cytostatic and cytocidal drug effects becomes obvious in plots of corrected T/C values versus time of incubation. The influence of the untreated control on the corrected T/C values and possible time courses of theoretical inhibition profiles (reflecting cytostatic, transient cytotoxic or cytocidal drug effects as well as development of resistance) and their relationship to the corresponding growth curves of drugtreated cells are discussed. Chemosensitivity assays with diethylstilbestrol dipropionate, tamoxifen, melphalan, cisplatinum, vinblastine, Adriamycin and 5-fluorouracil prove the theoretical considerations to be true for MDA-MB-231, MCF-7, T-47-D and ZR-75-1 human breast cancer cell lines in practice.

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Abbreviations

PBS:

phosphate-buffered saline

FCS:

fetal calf serum

NCS:

newborn calf serum

ER:

oestrogen receptors

PR:

progesterone receptor

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Author notes

  1. Herbert Birnböck

    Present address: Hoffmann-La Roche AG, Grenzacher Strasse 124, CH-4002, Basel, Switzerland

Authors and Affiliations

  1. Institut für Pharmazie, Universität Regensburg, Sonderforschungsbereich 234, W-8400, Regensburg, Federal Republic of Germany

    Günther Bernhardt, Herta Reile, Herbert Birnböck, Thilo Spruß & Helmut Schönenberger

Authors
  1. Günther Bernhardt
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  2. Herta Reile
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  3. Herbert Birnböck
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  4. Thilo Spruß
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  5. Helmut Schönenberger
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Bernhardt, G., Reile, H., Birnböck, H. et al. Standardized kinetic microassay to quantify differential chemosensitivity on the basis of proliferative activity. J Cancer Res Clin Oncol 118, 35–43 (1992). https://doi.org/10.1007/BF01192309

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  • DOI: https://doi.org/10.1007/BF01192309

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