Biological characteristics of interferon-r-induced resistant histiocytic lymphoma cell line U937

A brief exposure (for 6 h) of U937 cells to interferon (IFN)-gamma (500 U/ml) followed by a long term incubation of cells in normal medium for 8 or more weeks resulted in the induction of cells that were refractory to the anticellular and differentiating effects of not only IFN-gamma but also IFN-alpha and IFN-beta at concentrations up to 10(4) U/ml. In addition, the cells became insensitive to the potent differentiating effect of the phorbol ester--tumor promoting agent (TPA). However, the resistant cells retained their sensitivity to the antiviral effect of different IFNs and were fullu responsive to the induction of endonuclease 2',5'-oligoadenylate (2-5A) synthetase by IFN. Furthermore, the resistant cell population appeared to be homogeneous because clones derived from single cells from this population all exhibited the same resistant phenotype to IFN and TPA. These results suggest that induction of resistant U937 cells may involve a dedifferentiation process which results in the formation of an immature cell population that do not respond to the differentiating and/or anticellular effects of various types of IFNs.