BLEOMYCIN-INDUCED DIFFERENTIATION OF A HUMAN MONOBLAST CELL-LINE U937

Chemotherapeutic approaches to therapy of neoplastic diseases traditionally are directed at eliminating neoplastic cells by the cytotoxic effects of those agents. Recent evidence has suggested that, at least in part, the ability of some of those agents to induce differentiation of malignant cells has played a role in the elimination of those malignant populations. Bleomycin, an agent frequently used in cancer chemotherapy, has been shown to promote differentiation of erythroleukemia cells, We have examined the ability of bleomycin to differentiate a human, monoblast-like cell line (U937). Incubation of U937 in the presence of bleomycin for up to 96 hours resulted in changes in several parameters consistent with differentiation. A dose-dependent decrease in cell growth and increase in cell size was seen over the four-day culture period. Morphology was consistent with differentiation to a macrophage phenotype and increases in expression of nonspecific esterase (7-fold), phagocytosis (3-fold), and reduction of nitroblue tetrazolium (3-fold) further supported this line of differentiation. In addition,to these functional and morphologic changes, we have observed a decrease in expression of c-myc mRNA and increased mRNA for tumor necrosis factor, both of which are consistent with differentiation.