Summary
Of 39 human kidney carcinoma transplanted to nude mice, four tumor lines were maintained on nude mice by serial transplantation. The established tumor cell lines were used to determine the assay evaluability of three different drug-testing systems: the subrenal capsule assay (SRC), the in vitro assay with labeled DNA precursor (L-DNA-P) and the stem cell assay (STC). Tumor cell lines were used because they allowed us to perform the different assays with the same tumor. Criteria for assay evaluability were measurable growth of the transplanted tumor fragment (histologically proved) in the SRC-assay, the amount of thymidine incorporation in relation to the number of cells in vitro and time of incubation in the L-DNA-P-assay, and a mean colony count for the sixfold plated cells of 50 or greater in the STC-assay. The criteria for evaluability were fulfilled when athymic or irradiated immunocompetent mice were used for the SRC-assay. However, in immunocompetent, non-irradiated mice, remarkable incursion of host cells was found. In the L-DNA-P-assay, optimal incorporation was reached after different times of culture, with different cell numbers. Therefore the technique of assaying with labeled DNA precursor lacks optimally defined assay conditions. The tumor cell lines examined in the stem cell assay demonstrated excellent growth; they therefore may be useful for pharmacological studies of drug interactions.
Similar content being viewed by others
References
Agrez MV, Kovach JS, Lieber MM (1982) Cell aggregates in the soft agar “human tumour stem-cell assay”. Br J Cancer 46:880–887
Alley MC, Uhl CB, Lieber MM (1982) Improved detection of drug cytotoxicity in the soft agar colony formation assay through use of a metabolizable tetrazolium salt. Life Sci 31:3071–3078
Arai T, Okamoto K, Terao K, Tokita H, Sekimoto K, Fukushima T, Tanaka K (1977) Effectiveness of antitumor agents against human tumors in nude mice. Fischer, Stuttgart, pp 461–474 (Proc 2nd Int Workshop on Nude Mice)
Bogden AE, Kelton DE, Cobb WR, Esber HJ (1978) A rapid screening method for testing chemotherapeutic agents against human tumor xenografts. In: Houchens DP, Ovejera AA (eds) Proceedings of the Symposium on the Use of Athymic Nude Mice in Cancer Research. Fischer, New York Stuttgart, pp 231–250
Carney DN, Gazdar AF, Bunn PA Jr, Guccion IJ (1981) Demonstration of the stem-cell nature of clonogenic tumor cells from lung cancer patients. Stem Cells 1:149–164
Flanagan SP (1966) Nude, a new hairless gene with pleiotropic effects in the mouse. Genet Res 8:295–309
Fleischmann J, Heston WDW, Fair WR (1983) Renal cell carcinoma and the clonogenic assay. J Urol 130:1060–1062
Giovanella BC, Stehlin JS, Williams IJ, Lee SS, Shepard RC (1978) Heterotransplantation of human cancers into nude mice: a model system for human cancer chemotherapy. Cancer 42:2269–2281
Giovanella BC, Stehlin JS, Shepard RC, Williams LJ (1983) Correlation between response to chemotherapy of human tumors in patients and in nude mice. Cancer 52:1146–1152
Hagemeijer A, Höhn W, Smit EME (1979) Cytogenetic analysis of human renal carcinomal cell lines of common origin (NC-65). Cancer Res 39:4662–4667
Höhn WF, Schröder FH (1978) Renal cell carcinoma: two new cell lines and a serially transplantable nude mouse tumour (NC-65). Invest Urol 16:106–112
Johnson PA, Rossof AH (1983) The role of the human tumor stem cell assay in medical oncology. Arch Intern Med 143:111–114
Kurth KH, Weissglas GM, Romijn JC, Schröder FH, van Dongen JW (1983) In vitro and in vivo chemotherapeutic testing of human renal carcinoma in the nude mouse. Aktuel Urol 14:223–229
Lieber MM, Kovach JS (1981) Soft agar clonogenic assay for primary renal carcinoma: in vitro chemotherapy drug sensitivity testing. Invest Urol 19:111–114
Lieber MM (1984) Soft agar colony formation assay for in vitro chemotherapy sensitivity testing of human renal cell carcinoma: Mayo Clinic experience. J Urol 131:391–393
Nomura T, Ohsawa N, Tamaoki N, Fujiwara K (1977) List of human tumors transplanted to nude mice. Fischer, Stuttgart, pp 588–595 (Proc of the 2nd Int Workshop on Nude Mice)
Otto U, Klöppel G, Baisch H (1984) Transplantation of human renal cell carcinoma into NMRI nu/nu mice. I. Reliability of an experimental tumor model. J Urol 131:130–133
Pantelouris EM (1968) Absence of a thymus in a mouse mutant. Nature 217:370–371
Salmon SE, Hamburger AW, Soehnlen B, Durie BGM, Alberts DS, Moon TE (1978) Quantification of differential sensitivity of human tumor stem cells to anticancer drugs. N Engl J Med 298:1321–1327
Sarosdy MF, Lamm DL, Radwin HM, Von Hoff DD (1982) Clonogenic assay and in vitro chemosensitivity testing of human urologic malignancies. Cancer 50:1332–1338
Selby P, Heyderman E, Gibbs J, Peckham MJ (1979) A human testicular teratoma serially transplanted in immune-deprived mice. Br J Cancer 39:578–583
Selby P, Buick RN, Tannock I (1983) A critical appraisal of the “human tumor stem-cell assay”. N Engl J Med 308:129–134
Shrivastav S, Bonar RA, Stone KR, Paulson DF (1980) An in vitro assay procedure to test chemotherapeutic drugs on cells from human solid tumors. Cancer Res 40:4438–4442
Shorthouse AJ, Smyth JF, Steel GG, Ellison M, Mills J, Peckham MJ (1980) The human tumor xenograft — a valid model in experimental chemotherapy? Br J Surg 67:715–722
van Steenbrugge GJ, Blankenstein MA, Bolt-de Vries J, Romijn JC, Schröder FH, Vihko P (1983) Effect of hormone treatment on prostatic acid phosphatase in serially transplantable human prostatic adenocarcinoma (PC-82). J Urol 129:630–633
Trent JM, Salmon SE (1980) Human tumor karyology: marked analytic improvement by short-term agar culture. Br J Cancer 41:867–874
Von Hoff DD, Johnson E (1979) Secretion of tumor markers in the human tumor transplanted to nude mice. Proc Am Assoc Cancer Res/Am Soc Clin Oncol 20:51 (abstr)
Von Hoff DD, Casper J, Bradley E, Trent JM, Soehnlen B, Alberts D, Schmidt HJ (1980) Direct cloning of human neuroblastoma cells in soft agar culture. Cancer Res 49:3591–3597
Von Hoff DD (1983) Send this patient's tumor for culture and sensitivity. N Engl J Med 308:154–155
Author information
Authors and Affiliations
Additional information
Supported in part by a Grant from the “Nierstichting”, The Netherlands
Rights and permissions
About this article
Cite this article
Kurth, K.H., van Dongen, J.W., Romijn, J.C. et al. Assay evaluability of drug testing systems determined with human renal carcinoma cell lines. World J Urol 2, 146–155 (1984). https://doi.org/10.1007/BF00328096
Issue Date:
DOI: https://doi.org/10.1007/BF00328096