The effect of a growing tumor and its removal on the cytotoxicity of macrophages from cultured bone marrow cells.

Previous investigations by us have demonstrated that there is a significant but transient (4 to 14 days) increase of colony-forming cells (CFC) in bone marrow following implanation of a syngeneic mammary tumor in C3H mice. Those CFC gave rise to enhanced macrophage colony production when cultured in semisolid medium. The present studies have for the first time demonstrated that macrophages from the colonies were cytotoxic to cells from the immunizing tumor, and they continued to possess that characteristic for as long as a tumor was present in the animal from which bone marrow was derived. By 21 days after tumor removal cytotoxicity was no longer evident. The findings provide evidence to suggest that the cytotoxicity displayed by the macrophage originates in its ancestral CFC or in the antecedent stem cell. They also suggest that receptor sites of the CFC (or stem cell) that respond to a stimulus for self-replication are probably different from those sites that, when activated, result in cytotoxic properties of their progeny. The present findings also indicate not only that quantitation of macrophage production is of relevance in determining the efficacy of a therapeutic regimen but also that knowledge concerning the specific properties, i.e., ctytotoxicity, of such cells is of equal or greater importance.