Weakening of genetic resistance. II. The effect of injection of the macrophage toxic agents silica and carragheenan and the cytostatic drugs cyclophosphamide, busulphan and vinblastin.

Silica (4 mg/i.v.) and Carragheenan (20 mg/i.p.) were shown to be capable of weakening hybrid resistance in the spleen whereas no improved growth was observed in the femoral bone marrow. Histological data did not indicate that the agents in the doses used caused significant macrophage mortality. It was concluded that the weakening effect of the agents was not due to death of the effector cells but possibly to a stimulation of the mononuclear phagocytic system in the spleen. Cyclophosphamide (250 mg/kg) induced a weakening of hybrid resistance which was observed both in the spleen and the femoral bone marrow. Experiments with the alkylating agent Busulphan and with Vinblastin showed that both agents were only capable of inducing a moderate stimulation of growth of the transplant in the spleen. A direct specific influence of cyclophosphamide on the microenvironment was proposed. Xenogeneic resistance was studied by transplantation of rat bone marrow to mice. Silica and cyclophosphamide were shown to be capable of inducing a weakening of the resistance in the spleen. The development of the graft in the femoral bone marrow did not appear to be affected by the administration of silica or cyclophosphamide.