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Drug sensitivity of ten human tumor cell lines compared to mouse leukemia (L1210) cells

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Abstract

L1210 leukemia cells, because of their rapid growth rate in suspension culture and high growth fraction, are ideally suited to screen in vitro for cytotoxic compounds. Although L1210 cells may mimic rapidly growing tumors, they have not been effective in selecting agents active against slow growing solid tumors. We expected that cell lines originating from human solid tumors, because of their slower growth rate and lower S phase fraction, would be more drug resistant than L1210. Therefore, we compared ten human tumor cell lines (5 melanomas, 4 colon carcinomas and 1 small cell lung carcinoma) to L1210 growth inhibition by 9 anti-tumor drugs. Not one human tumor cell line was consistently more resistant to all nine drugs than L1210 when the cells were exposed to drugs for about 2 doubling times. The drug sensitivity of 2 cell lines (L1210 and SK MEL 28) was again determined after a short term (2 hr) exposure and using growth inhibition and cell survival as end points. For both end points these two cell lines exhibited a random pattern of sensitivity to the drugs tested. Cell kill showed an order of sensitivity different than growth inhibition. The implication of these findings for drug-screening is discussed.

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References

  1. Staquet MJ, Byar DP, Green SG, Rosencweig M: Clinical predictivity of transplantable tumor systems in the selection of new drugs for solid tumors: rationale for a three-stage strategy. Cancer Treat Rep 67:753–765, 1983

    Google Scholar 

  2. Devita VT, Oliverio VT, Muggia FM, Wiernik PW, Ziegler J, Goldin A, Rubin D, Henney J, Schepartz S: The drug development and clinical trials programs of The Division of Cancer Treatment, NCl. Cancer Clin Trials 2:195–216, 1979

    Google Scholar 

  3. Badiner GJ, Wallace TL, Culp JW, Adams EG, Hamilton RD, Li LH, Bhuyan BK: Characterization and drug sensitivity of several human tumor cell lines compared to L1210 (Abstr) Proc Amer Assoc Cancer Res 25:329, 1985

    Google Scholar 

  4. Creekmore SP, Zaharko DS: Modification of chemotherapeutic effects on L1210 cells using hematoporphyrin and light. Cancer Res 43:5252–5257, 1983

    Google Scholar 

  5. Adams EG, Crampton SL, Bhuyan BK: Effect of 7-con-O-methyl-nogarol on DNA synthesis, survival and cell cycle progression of Chinese hamster ovary cells. Cancer Res 41:4981–4987, 1981

    Google Scholar 

  6. Bhuyan BK: The acton of streptozotocin on mammalian cells. Cancer Res 30:2017–2023, 1970

    Google Scholar 

  7. Carey TE, Takahashi T, Resnick LA, Oettgen HF, Old LJ: Cell surface antigens of human malignant melanoma: mixed hemadsorption assays for humoral immunity to cultured autologous melanoma cells. Proc Natl Acad Sci 73:3278–3282, 1976

    Google Scholar 

  8. Fogh J, Fogh CM, Orfeo T: One hundred and twenty-seven cultured human tumor cell lines producing tumors in nude mice. J Natl Cancer Inst 59:221–226, 1977

    Google Scholar 

  9. Quinn LA, Woods LK, Merrick SB, Arabasz NM, Moore GE: Cytogenetic analysis of twelve human malignant melanoma cell lines. J Natl Cancer Inst 59:301–307, 1977

    Google Scholar 

  10. Herlyn M, Clark WH, Mastrangelo MJ, Guerry D, Elder DE, LaRossa D, Hamilton R, Bondi E, Tuthill R, Steplewski Z, Koprowski H: Specific immunoreactivity of hybridoma-secreted monoclonal anti-melanoma antibodies to cultured cells and freshly derived human cells. Cancer Res 40:3602–3609, 1980

    Google Scholar 

  11. Leibovitz A, Stinson JC, McCombs WB, McCoy CE, Mazur K, Mabry ND: Classification of human colorectal adenocarcinoma cell lines. Cancer Res 36:4562–4569, 1976

    Google Scholar 

  12. Drewinko B, Yang LY, Barlogie B, Romsdahl MM, Meistrich M, Mabahy MA, Giovanella B: Further biological characteristics of a human carcinoembryonic antigen producing colon carcinoma cell line. J Natl Cancer Inst 61:75–83, 1978

    Google Scholar 

  13. Simms E, Gazdar AF, Abrams PG, Minna JD. Growth of human small cell (oat cell) carcinoma of the lung in serum-free growth factor-supplemented medium. Cancer Res 40:4356–4363, 1980

    Google Scholar 

  14. Moore GE, Sandberg AA, Ulrich K: Suspension cell culture and in vivo and in vitro chromosome constitution of mouse leukemia L1210. J Natl Cancer Inst 36:405–421, 1966

    Google Scholar 

  15. Wiesenthal LM: In vitro assays in preclinical antineoplastic drug screening. Sem Oncol 8:362–376, 1981

    Google Scholar 

  16. Roper P, Drewinko B: A comparison of in vitro methods to determine drug-induced cell lethality. Cancer Res 36: 2182–2188, 1976

    Google Scholar 

  17. Bhuyan BK, Loughman BE, Fraser TJ, Day KJ: Comparison of different methods of determining cell viability after exposure to cytotoxic agents. Exptl Cell Res 97:275–280, 1976

    Google Scholar 

  18. Pavlik EJ, Flanigan RC, VanNagell JR, Hanson MB, Donaldson ES, Keaton K, Doss B, Kenady DF: Esterase activity, exclusion of propidium iodide, and proliferation of tumor cells exposed to antitumor agents: Phenomena relevant to chemosensitivity determination. Cancer Invest 3:413–426, 1985

    Google Scholar 

  19. Finlay GJ, Baguley BC: The use of human cancer cell lines as a primary screening system for antineoplastic compounds. Eur J Cancer Clin Oncol 20:947–954, 1984

    Google Scholar 

  20. Wilson WR, Tapp SM, Baguley BC: Differential growth inhibition of cultured mammalian cells: comparison of clinical antitumor agents and amsacrine derivative. Eur J Cancer Clin Oncol 20:383–389, 1984

    Google Scholar 

  21. Heppner GH, Dexter DS, DeNucci T, Miller FR, Calabresi P: Heterogeneity in drug sensitivity among tumor cell subpopulations of a single mammary tumor. Cancer Res 38:3758–3763, 1978

    Google Scholar 

  22. Barranco SC, Townsend GM, Quaraishi MA, Burger NL, Nevill HC, Howell KH, Boerwinkle WR: Heterogeneous responses of an in vitro model of human stomach cancer to anticancer drugs. Invest New Drugs 1:117–127, 1983

    Google Scholar 

  23. Carney DN, Mitchell JB, Kinsella TJ: In vitro radiation and chemotherapy sensitivity of established cell lines of human small cell lung cancer and its large cell morphological variants. Cancer Res 43:2806–2811, 1983

    Google Scholar 

  24. Shoemaker R, Wolpert-Defilippes M, Kern D, Lieber M, Milnick N, Miller W, Salmon S, Simon R, Venditti J, VonHoff D: Antitumor drug screening with a human tumor colony forming assay (HTCFA). (Abstr) Proc Amer Assoc Cancer Res 25:326, 1984

    Google Scholar 

  25. Corbett TH: A selective two-tumor soft agar assay for drug discovery. (Abstr) Proc Amer Assoc Cancer Res 25:325, 1984

    Google Scholar 

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Badiner, G.J., Hamilton, R.D., Li, L.H. et al. Drug sensitivity of ten human tumor cell lines compared to mouse leukemia (L1210) cells. Invest New Drugs 5, 219–229 (1987). https://doi.org/10.1007/BF00175291

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