Abstract
Mutant clones of mouse myeloid leukemic cells have been used to study the effect of mouse interferon on the expression of different cellular genes. The cell mutants, MGI^+^D^+^, MGI^+^D^−^ and MGI^−^D^−^, differed in their competence to be induced to undergo cell differentiation by the normal macrophage and granulocyte protein inducer MGI or the steroid hormone dexamethasone. The growth of all the clones tested was inhibited by interferon, but there was a 20‐fold difference in sensitivity to growth inhibition in different clones. This difference was not associated with the same difference in susceptibility to the cytotoxic effect of cytosine arabinoside and actinomycin D, or with cell competence for the induction of differentiation. The variation in cytotoxic effect of interferon on different malignant cell populations should, therefore, be taken into consideration in the possible clinical use of interferon as an anti‐tumor agent. Some MGI^+^D^+^ clones, but none of the MGI^+^D^−^ or MGI^−^D^−^ clones, showed, in addition to a high sensitivity to growth inhibition by interferon, a 14‐ and 2‐fold enhancement of the induction of lysozyme by dexamethasone and MGI, respectively, and a slight induction of Fc rosettes with dexamethasone. But interferon had no effect on induction of C3 rosettes, immune phagocytosis and differentiation to mature macrophages or granulocytes. The enhancing effect on lysozyme induction by interferon was also obtained with cordycepin, vinblastine, or 2‐deoxy‐D‐glucose, although neither interferon nor any of these other compounds alone induced any of the differentiation‐associated properties. A MGI^+^D^−^ mutant, derived from an MGI^+^D^+^ clone with an enhancement of lysozyme induction by interferon, showed the same high sensitivity to growth inhibition by interferon as its parental MGI^+^D^+^ clone, but there was no enhancement of the induction of lysozyme by MGI or dexamethasone. The results indicate that interferon can exert a selective enhancing effect on the expression of some genes involved in differentiation in clones with the appropriate genotype and that, by using appropriate cell mutants, it is possible to genetically dissociate different cellular effects of interferon.