Hemopoietic progenitor cells are sensitive to the cytostatic effect of pyruvate

Abstract

The addition of certain oxidizable substrates (such as pyruvate and oxalacetate) produced a marked diminution of the number of colonies formed in vitro by mouse bone marrow cells (BMC) stimulated by spleen cell-conditioned medium (SCM). Pyruvate apparently exerted an all-or-none inhibition on colony forming cells (CFCs), affecting neither the size nor morphology of detectable colonies, which were essentially composed of immature cells, neutrophils, and monocytes-macrophages. Pyruvate furthermore reduced BMC proliferation in SCM-stimulated liquid cultures, apparently without modifying the cell population's morphological profile. The effects of pyruvate on hemopoietic progenitor cells were further studied by replating aliquots of BMC liquid cultures with or without pyruvate into agar medium devoid of this substrate. Pyruvate did not interfere with the increase in CFC number observed in the controls during the first few days of incubation, indicating that CFC generation is not inhibited by this substrate. However, the plating efficiency of CFCs recovered from liquid cultures with or without pyruvate was strongly inhibited when these cells were seeded into pyruvate-containing agar plates, thus supporting the theory that CFCs generated in vitro in both conditions have the same sensitivity to pyruvate as those originally present in bone marrow. On the whole, our results indicated that the pyruvate cytostatic effect is a metabolic feature distinguishing CFCs from their progenitors. These differences are discussed in the light of the explanation advanced for the pyruvate cytostatic effect in other cell systems.