Effect of Corynebacterium parvum on the proliferative rate of granulocyte-macrophage progenitor cells and the toxicity of chemotherapy.

We have studied the interaction of Corynebacterium parvum and a variety of cell cycle-specific and cell cycle-nonspecific chemotherapeutic agents on granulocyte-macrophage progenitor cells [colony-forming units culture (CFU-c)] in C57BL/6 mice. In vitro tritiated thymidine suicide studies showed an increased rate of proliferation of bone marrow CFU-c 24 hr after C. parvum injection. In vivo toxicity of cell cycle-specific agents but not of cell cycle-nonspecific agents for bone marrow CFU-c was increased 24 hr after C. parvum injections. The increased numbers of CFU-c in the spleen, induced by C. parvum, were also sensitive to a cell cycle-specific agent for up to 7 days after C. parvum injection. The findings suggest differences in the kinetics of proliferation of splenic compared to bone marrow CFU-c. The relative time of administration of chemotherapy and immunostimulants such as C. parvum will have to be carefully considered in the design of clinical trials.