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Survival of human bone marrow cells after in vitro treatment with 12 anticancer drugs and implications for tumor drug sensitivity assays

  • Original Papers
  • Clinical Oncology or Epidemiology
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Summary

We investigated the responsiveness of human normal granulocyte-macrophage colony-forming units in culture (GM-CFUC) continuously exposed in vitro to 1 of 12 anticancer drugs. All drugs except bleomycin showed a simple negative exponential dosesurvival curve. The in vitro toxicity of drugs in GM-CFUC did not always correlate with the relative myelosuppressive potency observed in vivo. In addition, tumor specimens from 38 patients mainly with ovarian cancer were cultured in a human tumor colony-forming assay and continuously exposed to drugs at low, intermediate, and high concentrations capable of killing 40%, 78%, and 99% of GM-CFUC, respectively. The most active drugs were cis-platinum, velban, 5-fluorouracil, and 5-fluoro-ara-AMP. Dosesurvival curves of bone marrow progenitor cells may serve as an in vitro reference system for selecting appropriate drug concentrations of myelosuppressive drugs in drug-sensitivity assays of human tumors.

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References

  • Alberts DS, Chen HSG, Salmon SE (1980) In vitro drug assays: Pharmacologic considerations. In: Salmon SE (ed) Cloning of human tumor stem cells. Alain R Liss, New York, pp 197–207

    Google Scholar 

  • Barranco SC (1978) A review of the survival and cell-kinetics of bleomycin. In: Carter SK, Crooke ST, Umezawa H (eds) Bleomycin: current status and new developments. Academic Press, New York, pp 81–90

    Google Scholar 

  • Drewinko B, Novak JK, Barranco SC (1972) The response of human lymphoma cells in vitro to bleomycin and 1,3-bis(chloroethyl)-1-nitrosurea. Cancer Res 32:1206–1208

    Google Scholar 

  • Hahn GM (1978) Radiobiological techniques applied to environmental problems. Radiat Res. 76:459–470

    Google Scholar 

  • Hug V, Thames H, Spitzer G, Blumenschein GR, Drewinko B (1984) Normalization of in vitro sensitivity testing of human clonogenic cells. Cancer Res (in press)

  • Kaufmann M, Kubli F (1978) Resistenztestung menschlicher Tumor und Knochenmarkszellen gegenüber Zytostatika. Fortschr Med 96:823–826

    Google Scholar 

  • Kern DH, Bertelsen CA, Maan BD, Campbell MA, Morton DL, Cochran AJ (1983) Clinical application of the clonogenic assay. Ann Clin Lab Sci 13:10–15

    Google Scholar 

  • Lohrmann HP, Schreml W, Lang M, Betzler M, Fliedner TM, Heimpel H (1978) Changes of granulopoeisis during and after adjuvant chemotherapy of breast cancer. Br J Haematol 40:369–381

    Google Scholar 

  • Lohrmann HP, Lepp KA, Schreml W (1982) 5-Fluorouracil, 1,3-bis(2-chloroethyl)-1-nitrosurea, and 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosurea: Effect of the human granulopoietic system. JNCI 68:541–547

    Google Scholar 

  • Nothdruft M, Bruch C, Fliedner TM, Ruber E (1977) Studies on the regeneration of the CFU-C population in blood and bone marrow of lethally irradiated dogs after autologous transfusion of cryopreserved mononuclear cells. Scand J Haematol 19:470–481

    Google Scholar 

  • Ozawa K, Miura Y, Suda T, Motoyoshi K, Takaku (1983) Radiation sensitivity of leukemic progenitor cells in acute nonlymphatic leukemia. Cancer Res 43:2339–2341

    Google Scholar 

  • Park CH, Wiernik PH, Morrison FS, Amare M, Van Sloten K, Maloney TR (1983) Clinical correlations of leukemic clonogenic cell sensitivity assessed by in vitro continuous exposure to drugs. Cancer Res 43:2346–2349

    Google Scholar 

  • Pinedo HM, Zaharko DS, Bull J, Chabner BA (1976) The reversal of methotrexate cytotoxicity to mouse bone marrow cells by leucovorin and nucleosides. Cancer Res 36:4418–4424

    Google Scholar 

  • Rosenblum ML, Dougherty DV, Reese C, Wilson CB (1981) Potentials and pitfalls of human stem cell analysis. Cancer Chemother Pharmacol 6:227–235

    Google Scholar 

  • Salmon SE, Von Hoff DD (1981) In vitro evaluation of anticancer drugs with the human tumor stem cell assay. Semin Oncol 8:377–385

    Google Scholar 

  • Stewart DJ, Benjamin RS, Luna M, Feun L, Caprioli R, Seifert W, Loo TL (1982) Human tissue distribution of cis-platinum after cis-diamminedichloroplatinum. Cancer Chemother Pharmacol 10:51–54

    Google Scholar 

  • Terasima T, Watanabe M, Takabe Y (1979) Upward concave doserelationship in bleomycin lethality of mammalian cells. In: Hecht (ed) Bleomycin: chemical, biochemical and biological aspects. Springer, New York, pp 297–308

    Google Scholar 

  • Thigpen JT, Lagasse L, Homesley H, Blessing JA (1983) Cisplatinum in the treatment of advanced or recurrent adenocarcinoma of the ovary. Am J Clin Oncol 6:431–435

    Google Scholar 

  • Twentyman PR, Blehen NM (1973) The sensitivity to bleomycin of spleen colony forming units in the mouse. Br J Cancer 28:66–70

    Google Scholar 

  • Umbach G, Spitzer G, Thames H, Hug V, Rudolph F, Drewinko B (1984) Factors determining methotrexate cytotoxicity in human bone marrow progenitor cells: Implications for in vitro drug testing of human tumors. In: Salmon SE, Trent JM (eds) Proceedings of the Fourth Conference on Human Tumor Cloning. Grune and Stratton, Orlando (in press)

    Google Scholar 

  • Verma DS, Spitzer G, Beran M, Zander A, McCredie KB, Dicke K (1980) Colony stimulating factor: augmentation in human placental conditioned medium. Exp Hematol 8:917–923

    Google Scholar 

  • Von Hoff DD, Clark GM, Stogdill BJ, Sarosdy MF, O'Brien MT, Casper JT, Mattox DE, Page CP, Cruz AB, Sandbach JF (1983) Prospective clinical trial of a human tumor cloning system. Cancer Res 1926–1931

  • Williams TJ, Lieber MM, Podratz KC, Malkasian GD (1983) Soft agar colony formation assay for in vitro testing of sensitivity to chemotherapy of gynecologic malignancies. Am J Obstet Gynecol 145:940–945

    Google Scholar 

  • Young RC, Van Hoff DD, Gormley P, Makuch R, Casidy J, Howser D, Bull JM (1979) Cis-dichlorodiammineplatinum(II) for the treatment of advanced ovarian cancer. Cancer Treat Rep 63:1539–1544

    Google Scholar 

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This work was supported by NIH grants CA 28153, CA 14528, CA 23272, the Max Kade Foundation, New York, and the Leukemia Society of America

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Umbach, G.E., Hug, V., Spitzer, G. et al. Survival of human bone marrow cells after in vitro treatment with 12 anticancer drugs and implications for tumor drug sensitivity assays. J Cancer Res Clin Oncol 109, 130–134 (1985). https://doi.org/10.1007/BF00391887

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  • DOI: https://doi.org/10.1007/BF00391887

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