A glucocorticoid-sensitive clonal cell line (CEM-C7) derived from the human CCRF-CEM lymphoblastoid cell line has been exploited to investigate the actions of and interactions among some standard drugs used for the chemotherapy of acute lymphoblastic leukemia. Cell viability was determined by measuring the ability of cells to form colonies in agarose gel, and the distribution of cells in various phases of the cell cycle was measured by flow microfluorometry. After exposure to 10-6m prednisolone, cells of the CEM-C7 clone began to die and concomitantly to accumulate in the G1 phase of the cell cycle after 18 to 24 hr of exposure. Dose-response curves were also obtained for the killing effects of methotrexate, vincristine, and 6-mercaptopurine, either after 24 hr or with continuous exposure to the drug. The toxicity of each of these drugs was about that expected from plasma concentrations achieved during chemotherapy of acute lymphoblastic leukemia. The possibility that prednisolone might exert inhibitory or synergistic effects when used in conjunction with the other drugs was investigated by incubating cells in 10-6m prednisolone for 24 hr, followed by an additional 24 hr in prednisolone and either methotrexate (5 × 10-6m), vincristine (5 × 10-9m), or 6-mercaptopurine (10-5m). The combination of either vincristine or methotrexate with prednisolone showed a slight degree of synergism. The combination of prednisolone and 6-mercaptopurine, however, had an effect which was less than additive, suggesting that one of these drugs inhibits the action of the other.

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Presented at the John E. Fogarty International Center Conference on Hormones and Cancer, March 29 to 31, 1978, Bethesda, Md.

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