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Effect of Treatment with 1,3-Bis(2-chloroethyl)-1-nitrosourea or Cyclophosphamide on Spleen Colony-forming Units and Survival Time of Leukemic Mice¹

Microbiological Associates, Incorporated [S. V., V. S. W., J. N. C.] and Cancer Chemotherapy National Service Center, National Cancer Institute [A. G.], Bethesda, Maryland 20014

The effect of treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU, NSC 409,962) or cyclophosphamide (NSC 26,271) on spleen and bone marrow tissues of mice bearing leukemia (L1210) and normal mice was investigated. Donor mice with ascites L1210 were given a single treatment on Day 3 with BCNU (20 or 30 mg/kg) or cyclophosphamide (75, 150, 300, or 450 mg/kg). The survival time of the animals was determined, and the fate of leukemic cells in treated and untreated control mice was examined by spleen colony and survival time assays of spleen and bone marrow cells in recipient mice. Spleen and bone marrow tissues of treated and control normal nonleukemic mice were also assayed for colony-forming units (CFU).

Optimal doses of BCNU (30 mg/kg) and cyclophosphamide (300 mg/kg) increased the median survival time of the treated mice more than 200% over controls. The effect of these drugs appeared to be more pronounced on the leukemic cells than on the normal spleen and bone marrow cells. The effect of BCNU was relatively long-lasting for the leukemic and normal cells of the spleen, whereas cyclophosphamide was more effective on the cells in the bone marrow. The ability of the drugs to increase the survival time of the animals was reflected in suppression of CFU formation and in decreased growth of leukemic spleen and bone marrow cells implanted in recipient mice. The usefulness of the CFU and retransplant bioassays in recipient mice is discussed in relation to the determination of the influence of drugs on sequestered sites, the rate of growth of the leukemic cell population, and the determination of optimal procedures for drug administration.

¹ This study was supported by Contract PH-43-64-911 from the Cancer Chemotherapy National Service Center, National Cancer Institute, NIH, USPHS.

Received 11/13/67. Accepted 4/ 1/68.