This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tanigawa, N. Articles by Morton, D. L. Search for Related Content PubMed PubMed Citation Articles by Tanigawa, N. Articles by Morton, D. L.

Rapid Assay for Evaluating the Chemosensitivity of Human Tumors in Soft Agar Culture¹

Surgical Service, Veterans Administration Medical Center, Sepulveda, California 91343 [N. T., D. H. K., D. L. M.]; Division of Surgical Oncology, John Wayne Clinic, UCLA School of Medicine, Los Angeles, California 90024 [N. T., D. H. K., D. L. M.], and Department of Surgery, University of Kyoto, Sakyo-ku, Kyoto, Japan [Y. H.]

Assays that measure [³H]thymidine incorporation by cells plated in soft agar were investigated to identify a rapid method for assessing chemosensitivity of tumor cells. Six established cell lines (five melanomas and one colon carcinoma) and cells prepared from 23 primary or metastatic tumors (ten melanomas, five colon adenocarcinomas, three lung carcinomas, two ovarian adenocarcinomas, one breast adenocarcinoma, and one leiomyosarcoma) were tested. The end point of tritium incorporation was measured by autoradiographs (labeling index) and scintillation counting (cpm) after 24-hr labeling. When results were compared, there was a strong correlation between the two assays (p < 0.0001).

However, the scintillation counting assay had major advantages: (a) counting incorporated radioisotope was technically easier than the autoradiographic method; (b) the DNA synthesis rate of the whole tumor cell population could be evaluated, not that of tumor colony-forming cells alone; and (c) the sampling error was minimized since the procedure was done automatically. There was significant association between cpm values 48 to 72 hr after plating and the number of colonies formed at 2 to 4 weeks in control dishes (p < 0.001). Eighteen of 23 surgical specimens (78%) and all four cell lines were evaluable. Chemosensitivity was assessed after 48 hr of plating with alkylating agents, antibiotics, and Vinca alkaloids and after 72 hr with 5-fluorouracil and methotrexate. Results of 93 courses of drug-related inhibition of colony formation were compared to results of the scintillation assay. Results suggested that an 80% or greater reduction of [³H]thymidine incorporation was correlated with a 75% or greater decrease in colony growth (p < 0.0001). Thus, this scintillation assay accurately predicted drug-tumor interactions within 5 days that resulted in a 75% or greater decrease in colonies.

¹ Supported by Veterans Administration Medical Research Service.

² Present address: Department of Surgery, University of Kyoto, Sakyo-ku, Kyoto, Japan. To whom requests for reprints should be addressed, at the Division of Surgical Oncology, Ninth Floor, Factor Building, UCLA School of Medicine, Los Angeles, Calif. 90024.

Received 7/ 6/81. Accepted 3/ 2/82.

This article has been cited by other articles:

				K. Maruno, A. Absood, and S. I. Said Vasoactive intestinal peptide inhibits human small-cell lung cancer proliferation in vitro and in vivo PNAS, November 24, 1998; 95(24): 14373 - 14378. [Abstract] [Full Text] [PDF]

				Y. Lavie, H.-t. Cao, A. Volner, A. Lucci, T.-Y. Han, V. Geffen, A. E. Giuliano, and M. C. Cabot Agents that Reverse Multidrug Resistance, Tamoxifen, Verapamil, and Cyclosporin A, Block Glycosphingolipid Metabolism by Inhibiting Ceramide Glycosylation in Human Cancer Cells J. Biol. Chem., January 17, 1997; 272(3): 1682 - 1687. [Abstract] [Full Text] [PDF]