Combined therapy of leukemia La with Damvar and cytostatics.

The new cytostatic drug Damvar, delta-(2-amino-6-hydroxy-3,4-dihydro-4-oxo-5-pyrimidinyl)valeric acid, is not effective in La leukemia system. Damvar given in combination with 5-fluorouracil enhanced the anti-La effect of 5-Fu. There was also enhancement of the antileukemic effect of suboptimal and optimal doses of cyclophosphamide with the addition of Damvar.

Antileukemic effects of 5-(2-dimethylaminoethoxy)-7-oxo-7H-benzo(c) fluorene, substance VUFB 13 468, on L1210 and La leukemia.

The antineoplastic effect of 5-(2-dimethyl-aminoethoxy)-7-oxo-7H-benzo(c) fluorene, substance VUFB 13 468, was studied in leukemia L1210 and leukemia La. It was found that the test substance, in the form of base and in the form of hydrochloride, influenced favorably the survival of leukemic mice, in which the life span increased in dependence on the dose and the scheme of its application.

Combined therapy of L1210 leukemia with Damvar and cytostatics.

Damvar, the delta-(2-amino-6-hydroxy-3,4-dihydro-4-oxo-5-pyrimidinyl) valeric acid, administered alone s. c. or i. p., has no effect on L1210 leukemia. In DBA2 mice with L1210, Damvar administered in combination with 5-fluorouracil, or with 6-mercaptopurine, or with cyclophosphamide, in optimal doses, enhances or intensifies the antileukemic effects of the above cytostatics.

Derivatives of benzo(c)fluorene. XI. Effect of Benfluron on hemopoietic stem cells.

The effect of Benfluron-- 5-(2-N,N-dimethylamino-ethoxy)-7-oxo-7H-benzo(c)fluorene hydrochloride--on hemopoietic stem cells was tested by the production of spleen cell colonies (CFU-S) in irradiated mice following application of bone marrow cells and by the production of hemopoietic colonies (CFU-C) in semisolid agar. The reduced numbers of CFU-S were found in mice applied Benfluron or Benfluron-treated bone marrow cells. The increased numbers of CFU-S, however, were found in mice receiving bone marrow cells from Benfluron-treated donors. The production of CFU-C was decreased after 2 h incubation of bone marrow cells with 0.5-5 micrograms/ml of Benfluron, and fully inhibited at higher concentrations.

Derivatives of benzo(c)fluorene. X. Inhibitory effect of Benfluron on cellular immunity.

The effect of a cytostatic drug Benfluron-- 5(2-N,N-dimethyl-amino-ethoxy)-7-oxo-7H-benzo(c)fluorene hydrochloride was tested in mice on skin graft survival, graft-versus-host reaction (GVHR) and for mitogenic stimulation of human lymphocytes. Application of Benfluron resulted in a prolonged skin graft survival. The regional and systemic GVHR was potentially inhibited by p. o. administration of Benfluron at a dose of 100 mg/kg of body weight. Allogeneic spleen cells incubated with Benfluron at concentration of 5-20 micrograms/ml showed reduced capability to induce GVHR. PHA or PWM stimulation of lymphocytes was completely inhibited in the presence of 2 micrograms/ml Benfluron. Benfluron as a potent immunosuppressive agent can be considered useful for the prevention of GVHR.

The effect of Damvar on the formation of hemopoietic splenic colonies in mice, and on the peripheral blood picture in rats and dogs.

The present paper deals with the effect of Damvar on hemopoiesis. The test of formation of hemopoietic splenic colonies (CFU-S) was used in mice, the peripheral blood picture and bone marrow differential after long-term administration of Damvar was tested in rats and dogs. The bone marrow cells from mice after a single dose of Damvar or cells incubated with Damvar in vitro showed no reduction of colony-forming activity. A single dose or repeated variable doses of Damvar, or combined administration of Damvar and Cyclophosphamide in some cases influenced the number of CFU-S in irradiated mice following transplantation of normal murine bone marrow cells. A number of CFU-S lower than 75% of the control count was never found. The application of Damvar to rats and dogs caused no significant changes in their blood pictures and bone marrows.