Clonal regulation of the induction of macrophage-and granulocyte-inducing proteins for normal and leukemic myeloid cells.

A cloned line of myeloid leukemic cells can be induced by the alkylating agent nitrosoguanidine for two macrophage- and granulocyte-inducing (MGI) activities. One activity, MGI-I, induced the formation of macrophage and granulocyte colonies from normal myeloblasts. Another activity, MGI-2, induced differentiation of MGI+D+ myeloid leukemic cells to macrophages and granulocytes. Experiments on the time course of induction of the two activities have shown that MGI-I was induced before MGI-2, MGI-1 was first detected in cell extracts and this was followed by detection of both activities in culture supernatants (conditioned medium). After induction with bacterial lipopolysaccharide, another inducer of both MGI activities in this clone, MGI-I was also detected before MGI-2 in cell extracts. The steroid dexamethasone, which is an effective inducer of some differentiation-associated properties in this clone, did not induce either MGI-1 or MGI-2. Studies with different clones of myeloid leukemic cells have shown a clonal variation in the induction of MGI-1 and MGI-2. Different clones were induced by nitrosoguanidine either for MGI-1 and MGI-2, for MGI-1 without MGI-2, or for neither MGI-1 nor MGI-2. None of the clones were induced for MGI-2 without MGI-1. The results indicate that the induction of MGI-1 and MGI-2 is differently regulated in the same clone, and that there is a clonal and thus presumably genetic variation in inducibility for these two activities of MGI.