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Cell Proliferation Kinetics and Drug Sensitivity of Exponential and Stationary Populations of Cultured L1210 Cells¹

The Upjohn Company, Kalamazoo, Michigan 49001

Drug sensitivity and cell cycle parameters of L1210 cells in culture in exponential (10⁵ to 4 x 10⁵ cells/ml) and plateau phase (>8 x 10⁵ cells/ml) of growth were compared.

The percentage of cells in G₁, S, and G₂ + M for exponential and plateau-phase cultures was 24.1, 70.0, and 5.9, and 42.5, 45.6, and 11.9, respectively. These values correspond to those reported previously for early and late L1210 mouse leukemia cells. Cell survival (measured by cloning) after drug exposure showed that actinomycin D, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, chlorozotocin, and streptozocin were all equally lethal to cells in both phases, and 1-ß-D-arabinofuranosylcytosine, high-specific-activity (20 Ci/mmole) [³H]thymidine, vincristine, daunomycin, adriamycin, and 5-fluorouracil were more lethal to exponential cells than to plateau-phase cells. The percentage kill by S-phase-specific agents such as 1-ß-D-arabinofuranosylcytosine and [³H]thymidine corresponded well with the percentage of cells in S. Finally, 1,3-bis(2-chloroethyl)-1-nitrosourea was more toxic to plateau cells than to exponential cells.

¹ This study was supported in part by Contract NO1-CM-43753 with the Division of Cancer Treatment, NIH, Department of Health, Education and Welfare.

Received 9/20/76. Accepted 12/29/76.